According to the United States Census Bureau, the city has a total area of 324.0 square miles (839.2 km), of which 315.1 square miles (816.0 km²) is land and 9.0 square miles (23.2 km), or 2.76%, is water.

Downtown Memphis rises from a bluff along the Mississippi River. The city and metro area spread out through suburbanization, and encompass southwest Tennessee, northern Mississippi, and eastern Arkansas. Several large parks were founded in the city in the early 20th century, notably Overton Park in Midtown and the 4,500-acre (18 km) Shelby Farms. The city is a national transportation hub and Mississippi River crossing for Interstate 40, (east-west), Interstate 55 (north-south), barge traffic, Memphis International Airport (FedEx's "SuperHub" facility) and numerous freight railroads that serve the city.

The Memphis Riverfront stretches along the Mississippi River from the Meeman-Shelby Forest State Park in the north, to the T. O. Fuller State Park in the south. The River Walk is a park system that connects downtown Memphis from Mississippi River Greenbelt Park in the north, to Tom Lee Park in the south.

In recent years, the city has decided to deannex some of its territory. It has gone through a three-phase process to deannex five areas within the city limits, returning them to unincorporated Shelby County. The first phase of deannexation occurred on January 1, 2020, when the Eads and River Bottoms areas returned to county jurisdiction. As a result, the Shelby County Sheriff is responsible for patrolling these former parts of Memphis. The first phase of the deannexation process reduced the city's size by 5% and its population by 0.03%.

Shelby County is located over four natural aquifers, one of which is recognized as the "Memphis Sand Aquifer" or simply as the "Memphis Aquifer". Located 350 to 1,100 feet (110 to 340 m) underground, this artesian water source is considered soft and estimated by Memphis Light, Gas and Water to contain more than 100 trillion US gallons (380 km) of water.

Memphis has a humid subtropical climate (Köppen Cfa, Trewartha Cf), with four distinct seasons, and is located in USDA Plant Hardiness Zone 8a in downtown, cooling to 7b for much of the surrounding region. Winter weather comes alternately from the upper Great Plains and the Gulf of Mexico, which can lead to drastic swings in temperature. Summer weather may come from Texas (very hot and humid) or the Gulf (hot and very humid). July has a daily average temperature of 82.8 °F (28.2 °C), with high levels of humidity due to moisture encroaching from the Gulf of Mexico. Afternoon and evening thunderstorms are frequent during summer, but usually brief, lasting no longer than an hour. Early autumn is pleasantly drier and mild, but can be hot until late October. Late autumn is rainy and cooler; precipitation peaks again in November and December. Winters are mild to chilly, with a January daily average temperature of 42.1 °F (5.6 °C). Snow occurs sporadically in winter, with an average seasonal snowfall of 2.7 inches (6.9 cm). Ice storms and freezing rain pose a greater danger, as they can often pull tree limbs down on power lines and make driving hazardous. Severe thunderstorms can occur at any time of the year though mainly during the spring months. Large hail, strong winds, flooding, and frequent lightning can accompany these storms. Some storms spawn tornadoes.

The lowest temperature ever recorded in Memphis was −13 °F (−25 °C) on December 24, 1963, and the highest temperature ever was 108 °F (42 °C) on July 13, 1980. Over the course of a year, there is an average of 4.4 days of highs below freezing, 6.9 nights of lows below 20 °F (−7 °C), 43 nights of lows below freezing, 64 days of highs above 90 °F (32 °C), and 2.1 days of highs above 100 °F (38 °C).

Memphis temperatures dropped to -4 F during the 1985 North American cold wave and during the December 1989 United States cold wave.

Annual precipitation is high (54.94 inches [1,400 mm]) and relatively evenly distributed throughout the year. Average monthly rainfall is especially high in March through May, and December, while August and September are relatively drier.

Occupying a substantial bluff rising from the Mississippi River, the site of Memphis has been a natural location for human settlement by varying indigenous cultures over thousands of years. In the first millennium A.D. people of the Mississippian culture were prominent; the culture influenced a network of communities throughout the Mississippi River Valley and its tributaries. The hierarchical societies built complexes with large earthwork ceremonial and burial mounds as expressions of their sophisticated culture. The Chickasaw people, believed to be their descendants, later inhabited this site and a large territory in the Southeast.

French explorers led by René-Robert Cavelier, Sieur de La Salle, and Spanish explorer Hernando de Soto encountered the historic Chickasaw in this area in the 16th century.

J. D. L. Holmes, writing in Hudson's Four Centuries of Southern Indians (2007), notes that this site was a third strategic point in the late 18th century through which European powers could control United States encroachment beyond the Appalachians and their interference with Indian matters—after Fort Nogales (present-day Vicksburg) and Fort Confederación (present-day Epes, Alabama): "Chickasaw Bluffs, located on the Mississippi River at the present-day location of Memphis. Spain and the United States vied for control of this site, which was a favorite of the Chickasaws."^: 71

In 1795 the Spanish Governor-General of Louisiana, Francisco Luis Héctor de Carondelet, sent his lieutenant governor, Manuel Gayoso de Lemos, to negotiate and secure consent from the local Chickasaw so that a Spanish fort could be erected on the bluff; Fort San Fernando De Las Barrancas was the result.^: 71 Holmes notes that consent was reached despite opposition from "disappointed Americans and a pro-American faction of the Chickasaws" when the "pro-Spanish faction signed the Chickasaw Bluffs Cession and Spain provided the Chickasaws with a trading post".

Fort San Fernando de las Barrancas remained a focal point of Spanish activity until, as Holmes summarizes:

The Spanish dismantled the fort, shipping its lumber and iron to their locations in Arkansas.

In 1796, the site became the westernmost point of the newly admitted state of Tennessee, in what was then called the Southwest United States. The area was still largely occupied and controlled by the Chickasaw nation. Captain Isaac Guion led an American force down the Ohio River to claim the land, arriving on July 20, 1797. By this time, the Spanish had departed. The fort's ruins went unnoticed 20 years later when Memphis was laid out as a city after the United States government paid the Chickasaw for land.

At the beginning of the century, as recognized by the United States in 1786 Treaty of Hopewell, the land still belonged to the Chickasaw Nation. In the Treaty of Tuscaloosa, signed in October 1818 and ratified by Congress on January 7, 1819, the Chickasaw ceded their territory in Western Tennessee to the United States. The city of Memphis was founded less than five months after the U.S. takeover of the territory, on May 22, 1819 (incorporated December 19, 1826), by John Overton, James Winchester and Andrew Jackson. They named it after the ancient capital of Egypt on the Nile River.

From the city's foundation onwards, African Americans formed large proportion of Memphis' population. Prior to the abolition of slavery in the United States, most Black people in Memphis were enslaved, being used as forced labor by white enslavers along the river or on outlying cotton plantations in the Mississippi Delta. The city's demographics changed dramatically in the 1850s and 1860s, due to waves of immigration and domestic migration. Due to increased immigration since the 1840s and the Great Famine, Irish Americans made up 9.9% of the population in 1850, but 23.2% by 1860, when the total population was 22,623.

Tennessee seceded from the Union in June 1861, and Memphis briefly became a Confederate stronghold. Union ironclad gunboats captured it in the naval Battle of Memphis on June 6, 1862, and the city and state were occupied by the Union Army for the duration of the war. Union commanders allowed the city to maintain its civil government during most of this period but excluded Confederate States Army veterans from office. This shifted political dynamics in the city as the war went on.

The war years contributed to additional dramatic changes in the city population. The Union Army's presence attracted many fugitive slaves who had escaped from surrounding rural plantations. So many sought protection behind Union lines that the Army set up contraband camps to accommodate them. Memphis's black population increased from 3,000 in 1860, when the total population was 22,623, to nearly 20,000 in 1865, with most settling south of the city limits.

The rapid demographic changes added to the stress of war and occupation and uncertainty about who was in charge, increasing tensions between the city's ethnic Irish policemen and black Union soldiers after the war. In three days of rioting in early May 1866, the Memphis Riots erupted, in which white mobs made up of policemen, firemen, and other mostly ethnic Irish Americans attacked and killed 46 blacks, wounding 75 and injuring 100; raped several women; and destroyed nearly 100 houses while severely damaging churches and schools in South Memphis. Much of the black settlement was left in ruins. Two whites were killed in the riot. Many blacks permanently fled Memphis afterward, especially as the Freedmen's Bureau continued to have difficulty in protecting them. Their population fell to about 15,000 by 1870, 37.4% of the total population of 40,226.

Historian Barrington Walker suggests that the Irish rioted against blacks because of their relatively recent arrival as immigrants and the uncertain nature of their own claim to "whiteness"; they were trying to distinguish themselves from blacks in the underclass. The main fighting participants were ethnic Irish, decommissioned black Union soldiers, and newly emancipated African-American freedmen. Walker suggests that most of the mob was not in direct economic conflict with the blacks, as by then the Irish had attained better jobs, but were establishing social and political dominance over the freedmen.

Unlike the disturbances in some other cities, ex-Confederate veterans were generally not part of the attacks against blacks in Memphis. As a result of the riots in Memphis, and a similar one in New Orleans, Louisiana in September, Congress passed the Reconstruction Act and the Fourteenth Amendment to the U.S. Constitution.

In the 1870s, a series of yellow fever epidemics devastated Memphis, with the disease carried by river passengers traveling by ships along the waterways. During the Yellow Fever Epidemic of 1878, more than 5,000 people were listed in the official register of deaths between July 26 and November 27. The vast majority died of yellow fever, making the epidemic in the city of 40,000 one of the most traumatic and severe in urban U.S. history. Within four days of the Memphis Board of Health's declaration of a yellow fever outbreak, 20,000 residents fled the city. The ensuing panic left the poverty-stricken, the working classes, and the African-American community at the most risk from the epidemic. Those who remained relied on volunteers from religious and physician organizations to tend to the sick. By the end of the year, more than 5,000 were confirmed dead in Memphis. The New Orleans health board listed "not less than 4,600" dead. The Mississippi Valley recorded 120,000 cases of yellow fever, with 20,000 deaths. The $15 million in losses caused by the epidemic bankrupted Memphis, and as a result, its charter was revoked by the state legislature.

By 1870, Memphis's population of 40,000 was almost double that of Nashville and Atlanta, and it was the second-largest city in the South after New Orleans. Its population continued to grow after 1870, even when the Panic of 1873 hit the US hard, particularly in the South. The Panic of 1873 resulted in expanding Memphis's underclasses amid the poverty and hardship it wrought, giving further credence to Memphis as a rough, shiftless city. Leading up to the outbreak in 1878, it had suffered two yellow fever epidemics, cholera, and malaria, giving it a reputation as sickly and filthy. It was unheard of for a city with a population as large as Memphis's not to have any waterworks; the city still relied for supplies entirely on collecting water from the river and rain cisterns, and had no way to remove sewage. The combination of a swelling population, especially of lower and working classes, and abysmal health and sanitary conditions made Memphis ripe for a serious epidemic.

Kate Bionda, an owner of an Italian "snack house", died of a fever on August 13, 1878. Hers was officially reported by the Board of Health, on August 14, as the first case of yellow fever in the city. A massive panic ensued. The same trains and steamboats that had brought thousands into Memphis, in five days carried away more than 25,000 refugees, more than half of the city's population. On August 23, the Board of Health finally declared a yellow fever epidemic in Memphis, and the city collapsed, hemorrhaging its population. In July of that year, the city had a population of 47,000; by September, 19,000 remained, and 17,000 of them had yellow fever. The only people left in the city were the lower classes, such as German and Irish immigrant workers and African Americans. None had the means to flee the city, as did the middle and upper-class whites of Memphis, and thus they were subjected to a city of death.

Immediately following the Board of Health's declaration, a Citizen's Relief Committee was formed by Charles G. Fisher. It organized the city into refugee camps. The committee's main priority was to separate the poor from the city and isolate them in refugee camps. The Howard Association, formed specifically for yellow fever epidemics in New Orleans and Memphis, organized nurses and doctors in Memphis and throughout the country. They stayed at the Peabody Hotel, the only hotel to keep its doors open during the epidemic. From there they were assigned to their respective districts. Physicians of the epidemic reported seeing as many as 100 to 150 patients daily.

The Episcopal Community of St. Mary at St. Mary's Episcopal Cathedral played an important role during the epidemic in caring for the lower classes. Already supporting a girls' school and church orphanage, the Sisters of St. Mary also sought to provide care for the Canfield Asylum, a home for black children. Each day, they alternated caring for the orphans at St. Mary's, delivering children to the Canfield Asylum, and taking soup and medicine on house calls to patients. Between September 9 and October 4, Sister Constance and three other nuns fell victim to the epidemic and died. They later became known as the Martyrs of Memphis.

At long last, on October 28, a killing frost struck. The city sent out word to Memphians scattered all over the country to come home. Though yellow fever cases were recorded in the pages of Elmwood Cemetery's burial record as late as February 29, 1874, the epidemic seemed quieted. The Board of Health declared the epidemic at an end after it had caused over 20,000 deaths and financial losses of nearly $200 million. On November 27, a general citizen's meeting was called at the Greenlaw Opera House to offer thanks to those who had stayed behind to serve, of whom many had died. Over the next year property tax revenues collapsed, and the city could not make payments on its municipal debts. As a result, Memphis temporarily lost its city charter and was reclassified by the state legislature as a Taxing District from 1878 to 1893. But a new era of sanitation was developed in the city, a new municipal government in 1879 helped form the first regional health organization, and during the 1880s Memphis led the nation in sanitary reform and improvements.

Perhaps the most significant effect of yellow fever on Memphis was in demographic changes. Nearly all of Memphis's upper and middle classes vanished, depriving the city of its general leadership and class structure that dictated everyday life, similar to that in other large Southern cities, such as New Orleans, Charleston, South Carolina, and Atlanta, Georgia. In Memphis, the poorer whites and blacks fundamentally made up the city and played the greatest role in rebuilding it. The epidemic had resulted in Memphis being a less cosmopolitan place, with an economy that served the cotton trade and a population drawn increasingly from poor white and black Southerners.

The 1890 election was strongly contested, resulting in white opponents of the D. P. Hadden faction working to deprive them of votes by disenfranchising blacks. The state had enacted several laws, including the requirement of poll taxes, that made it more difficult for them to register to vote and served to disenfranchise many blacks. Although political party factions in the future sometimes paid poll taxes to enable blacks to vote, African Americans lost their last positions on the city council in this election and were forced out of the police force. (They did not recover the ability to exercise the franchise until after the passage of civil rights legislation in the mid-1960s.) Historian L. B. Wrenn suggests the heightened political hostility of the Democratic contest and related social tensions contributed to a white mob lynching three black grocers in Memphis in 1892.^{: 124, 131}

Journalist Ida B. Wells of Memphis investigated the lynchings, as one of the men killed was a friend of hers. She demonstrated that these and other lynchings were more often due to economic and social competition than any criminal offenses by black men. Her findings were considered so controversial and aroused so much anger that she was forced to move away from the city. But she continued to investigate and publish the abuses of lynching.^: 131

Businessmen were eager to increase the city population after the losses of 1878–79, and supported the annexation of new areas; this measure was passed in 1890 before the census. The annexation measure was finally approved by the state legislature through a compromise achieved with real estate magnates, and the area annexed was slightly smaller than first proposed.^: 126

In 1893 the city was rechartered with home rule, which restored its ability to enact taxes. The state legislature established a cap rate. Although the commission government was retained and enlarged to five commissioners, Democratic politicians regained control from the business elite. The commission form of government was believed effective in getting things done, but because all positions were elected at-large, requiring them to gain majority votes, this practice reduced representation by candidates representing significant minority political interests.

In terms of its economy, Memphis developed as the world's largest spot cotton market and the world's largest hardwood lumber market, both commodity products of the Mississippi Delta. Into the 1950s, it was also the world's largest mule market. These animals were still used extensively for agriculture. Attracting workers from Southern rural areas as well as new European immigrants, from 1900 to 1950 the city increased nearly fourfold in population, from 102,350 to 396,000 residents.

Racist violence continued into the 20th century, with four lynchings between 1900 and the lynching of Thomas Williams in 1928.

The Ford Motor Company built cars in Memphis from 1913 until 1958/59.

A Firestone Tire and Rubber Company plant made tires in North Memphis from 1936 to 1982. The plant made 100 million tires.

A Tennessee Powder Company built an explosives powder plant to make TNT and gunpowder on a 6,000-acre site in Millington in 1940. The plant was built to make smokeless gunpowder for the British Armed Forces during World War II. In May 1941, DuPont (1802–2017) took over the plant, changed the name to the Chickasaw Ordnance Works, and produced powder for the United States Armed Forces. There were 8,000 employees. The plant was dismantled after the war in 1946.

From the 1910s to the 1950s, Memphis was a place of machine politics under the direction of E. H. "Boss" Crump. He gained a state law in 1911 to establish a small commission to manage the city. The city retained a form of commission government until 1967 and patronage flourished under Crump. Per the publisher's summary of L.B. Wrenn's study of the period, "This centralization of political power in a small commission aided the efficient transaction of municipal business, but the public policies that resulted from it tended to benefit upper-class Memphians while neglecting the less affluent residents and neighborhoods."^{[page needed]} The city installed a revolutionary sewer system and upgraded sanitation and drainage to prevent another epidemic. Pure water from an artesian well was discovered in the 1880s, securing the city's water supply. The commissioners developed an extensive network of parks and public works as part of the national City Beautiful movement, but did not encourage heavy industry, which might have provided substantial employment for the working-class population. The lack of representation in city government resulted in the poor and minorities being underrepresented. The majority controlled the election of all the at-large positions.

Memphis did not become a home rule city until 1963, although the state legislature had amended the constitution in 1953 to provide home rule for cities and counties. Before that, the city had to get state bills approved in order to change its charter and other policies and programs. Since 1963, it can change the charter by popular approval of the electorate.^: 194

During the 1960s, the city was at the center of the Civil Rights Movement, as its large African-American population had been affected by state segregation practices and disenfranchisement in the early 20th century. African-American residents drew from the civil rights movement to improve their lives. In 1968, the Memphis sanitation strike began for living wages and better working conditions; the workers were overwhelmingly African American. They marched to gain public awareness and support for their plight: the danger of their work, and the struggles to support families with their low pay. Their drive for better pay had been met with resistance by the city government.

Martin Luther King Jr. of the Southern Christian Leadership Conference, known for his leadership in the non-violent movement, came to lend his support to the workers' cause. King stayed at the Lorraine Motel in the city, and was assassinated by James Earl Ray on April 4, 1968, the day after giving his I've Been to the Mountaintop speech at the Mason Temple.

After learning of King's murder, many African Americans in the city rioted, looting and destroying businesses and other facilities, some by arson. The governor ordered Tennessee National Guardsmen into the city within hours, where small, roving bands of rioters continued to be active. Fearing the violence, more of the middle-class began to leave the city for the suburbs.

In 1970, the Census Bureau reported Memphis's population as 60.8% white and 38.9% black. Suburbanization was attracting wealthier residents to newer housing outside the city. After the riots and court-ordered busing in 1973 to achieve desegregation of public schools, "about 40,000 of the system's 71,000 white students abandon the system in four years." Today, the city has a majority African-American population.

Memphis is well known for its cultural contributions to the identity of the American South. Many renowned musicians grew up in and around Memphis and moved to Chicago and other areas from the Mississippi Delta, carrying their music with them to influence other cities and listeners over radio airwaves.^{[full citation needed]}

Former and current Memphis residents include musicians Elvis Presley, Jerry Lee Lewis, Muddy Waters, Carl Perkins, Johnny Cash, Robert Johnson, W. C. Handy, Bobby Whitlock, B.B. King, Howlin' Wolf, Isaac Hayes, Booker T. Jones, Eric Gales, Al Green, Alex Chilton, Justin Timberlake, Three 6 Mafia, the Sylvers, Jay Reatard, Zach Myers, and Aretha Franklin.

The International Harvester Company manufacturing plant opened in 1947 and closed in 1985. The plant made cotton harvesting equipment and Farm Tillage equipment. It once had 1,000 employees.

CBI Nuclear Company operated in Memphis for more than 20 years. Chicago Bridge & Iron Company, CBI, and General Electric built large nuclear reactor pressure vessels and other large structures in Memphis.

On December 23, 1988, a tanker truck hauling liquefied propane crashed at the I-40/I-240 interchange in Midtown and exploded, starting multiple vehicle and structural fires. Nine people were killed and ten were injured. It was one of Tennessee's deadliest motor vehicle accidents and eventually led to the reconstruction of the interchange where it occurred.

Schering-Plough Corporation became defunct in 2009. It is now a subsidiary of Merck & Co. Abe Plough founded Plough, Incorporated in Memphis in 1908. In 1971, the Schering Corporation merged with Plough, Inc.

On June 2, 2021, the remains of Confederate General and Ku Klux Klan leader Nathan Bedford Forrest were removed from a Memphis park.

On January 7, 2023, after a routine traffic stop, five African American police officers brutally beat a 29-year-old African American man, Tyre Nichols. Nichols died from his injuries in the hospital three days later. Officer body cam footage and local surveillance cameras captured the altercations, which were described as "heinous" and showed "a total lack of regard for human life", according to Memphis police chief Cerelyn "CJ" Davis. The officers were fired and charged with second-degree murder, aggravated kidnapping, and other crimes. The relatively rapid dismissal and prosecution of the offending officers were favorably perceived by Nichols's family, and Davis called it a "blueprint" for future incidents of police brutality nationwide. The incident also resulted in the disbanding of the city's "SCORPION" unit, which had been mandated with directly combating the most violent crimes in the city. All the officers charged with involvement in Nichols's death were members of the unit.

Interstate 40, Interstate 55, Interstate 22, Interstate 240, Interstate 269, and State Route 385 are the main expressways in the Memphis area. Interstates 40 and 55 cross the Mississippi River at Memphis from the state of Arkansas. Interstate 69 is a proposed interstate that, upon completion, would connect Memphis to Canada and Mexico.

I-40 is a coast-to-coast freeway that connects Memphis to Nashville and on to North Carolina to the east, and Little Rock, Arkansas, Oklahoma City, and the Greater Los Angeles Area to the west. I-55 connects Memphis to St. Louis and Chicago to the north, and Jackson, Mississippi and New Orleans to the south. I-240 is the inner beltway which serves areas including Downtown, Midtown, South Memphis, Memphis International Airport, East Memphis, and North Memphis. I-269 is the larger, outer interstate loop immediately serving the suburbs of Millington, Eads, Arlington, Collierville, and Hernando, Mississippi. It was completed in 2018.

Interstate 22 connects Memphis with Birmingham, Alabama, via northern Mississippi (including Tupelo) and northwestern Alabama. While technically not entering the city of Memphis proper, I-22 ends at I-269 in Byhalia, Mississippi, connecting it to the rest of the Memphis interstate system.

Interstate 69 is proposed to follow I-55 and I-240 through the city of Memphis. Once completed, I-69 will link Memphis with Port Huron, Michigan via Indianapolis, Indiana, and Brownsville, Texas via Shreveport, Louisiana and Houston, Texas.

A new spur, Interstate 555, also serves the Memphis metro area connecting it to Jonesboro, Arkansas.

Other important federal highways though Memphis include the east–west U.S. Route 70, U.S. Route 64, and U.S. Route 72; and the north–south U.S. Route 51 and U.S. Route 61. The former is the historic highway north to Chicago via Cairo, Illinois, while the latter roughly parallels the Mississippi River for most of its course and crosses the Mississippi Delta region to the south, with the Delta also legendary for Blues music.

Roadways

Memphis maintains 6,800 lane-miles of city roadways. The city collaborated with Google Cloud Platform and SpringML in February 2019 to test machine learning (ML) to improve public services. A key focus is pothole identification using TensorFlow technology. Public Works personnel completed 63,000 repairs, with around 7,500 of those reported by citizens to 311.

The Memphis Area Transit Authority provides local transit services around Memphis, including the MATA Trolley heritage streetcar system. Intercity bus service to the city is provided by Flixbus, Greyhound Lines, and Jefferson Lines.

A large volume of railroad freight moves through Memphis, because of its two heavy-duty Mississippi River railroad crossings, which carry several major east–west railroad freight lines, and also because of the major north–south railroad lines through Memphis which connect with such major cities as Chicago, St. Louis, Indianapolis, Louisville, New Orleans, Dallas, Houston, Mobile, and Birmingham.

By the early 20th century, Memphis had two major passenger railroad stations, which made the city a regional hub for trains coming from the north, east, south and west. After passenger railroad service declined heavily through the middle of the 20th century, the Memphis Union Station was demolished in 1969. The Memphis Central Station was eventually renovated, and it still serves the city. The only inter-city passenger railroad service to Memphis is the daily City of New Orleans train, operated by Amtrak, which has one train northbound and one train southbound each day between Chicago and New Orleans.

• BNSF Railway (BNSF)
• Canadian National Railway (CN) through subsidiary Illinois Central Railroad (IC)
• CSX Transportation (CSXT)
• Canadian Pacific Kansas City (CPKC)
• Norfolk Southern Railway (NS), including subsidiaries Alabama Great Southern Railroad (AGS), Central of Georgia Railroad (CG), Cincinnati, New Orleans and Texas Pacific Railway (CNTP), Tennessee Railway (TENN), and Tennessee, Alabama and Georgia Railway (TAG)
• R.J. Corman Railroad/Memphis Line (RJCM)
• Union Pacific Railroad (UP)

Amtrak (AMTK)

Memphis International Airport is the global "SuperHub" of FedEx Express, and has the largest cargo operations by volume of any airport worldwide, surpassing Hong Kong International Airport in 2021.

Memphis International ranks as the 41st busiest passenger airport in the US and served as a hub for Northwest Airlines (later Delta Air Lines) until September 3, 2013. and had 4.39 million boarding passengers (enplanements) in 2011, an 11.9% decrease over the previous year. Delta has reduced its flights at Memphis by approximately 65% since its 2008 merger with Northwest Airlines and operates an average of 30 daily flights as of December 2013, with two international destinations (Cancún – seasonally; Toronto year-round). Delta Air Lines announced the closing of its Memphis pilot and crew base in 2012. Other airlines providing passenger service are: Southwest Airlines; American Airlines; United Airlines; Allegiant; Frontier; Air Canada; and Southern Vacations Express.

There are also general aviation airports in the Memphis Metropolitan Area, including the Millington Regional Jetport, located at the former Naval Air Station in Millington, Tennessee.

Memphis has the second-busiest cargo port on the Mississippi River, which is also the fourth-busiest inland port in the United States. The International Port of Memphis covers both the Tennessee and Arkansas sides of the Mississippi River from river mile 725 (km 1167) to mile 740 (km 1191). A focal point of the river port is the industrial park on President's Island, just south of Downtown Memphis.

Four railroad and highway bridges cross the Mississippi River at Memphis. In order of their opening years, these are the Frisco Bridge (1892, single-track rail), the Harahan Bridge (1916, a road-rail bridge until 1949, currently carries double-track rail), the Memphis-Arkansas Memorial Bridge (Highway, 1949; later incorporated into Interstate 55), and the Hernando de Soto Bridge (Interstate 40, 1973). A bicycle/pedestrian walkway opened along the Harahan Bridge in late 2016, utilizing the former westbound roadway.

Memphis's primary utility provider is the Memphis Light, Gas and Water Division (MLGW). This is the largest three-service municipal utility in the United States, providing electricity, natural gas, and pure water service to all residents of Shelby County. Prior to that, Memphis was served by two primary electric companies, which were merged into the Memphis Power Company.

The City of Memphis bought the private company in 1939 to form MLGW, which was an early customer of electricity from the Tennessee Valley Authority (TVA). In 1954 the Dixon-Yates contract was proposed to make more power available to the city from the TVA, but the contract was cancelled; it had been an issue for the Democrats in the 1954 Congressional elections.

MLGW still buys most of its power from TVA, and the company pumps its own fresh water from the Memphis Aquifer, using more than 180 water wells.

The Memphis and Shelby County region supports numerous hospitals, including the Methodist and Baptist Memorial health systems, two of the nation's largest private hospitals. Until the 1960s and the end of segregation, most hospitals only served white patients. One of the few hospitals for African Americans in Memphis in those times was Collins Chapel Connectional Hospital, whose historic building now houses a homeless shelter.

Methodist Le Bonheur Healthcare, the largest healthcare provider in the Memphis region and the fourth largest employer as of 2018, operates seven hospitals and several rural clinics. Methodist Healthcare operates, among others, the Le Bonheur Children's Hospital, which offers primary level 1 pediatric trauma care, as well as a nationally recognized pediatric brain tumor program. Methodist Healthcare also operates Methodist University Hospital, a 617-bed facility 1 mile southeast of Le Bonheur.

Baptist Memorial Healthcare operates fifteen hospitals (three in Memphis), including Baptist Memorial Hospital, and with a merger in 2018 became the largest healthcare system in the mid-South. According to Health Care Market Guide's annual studies, Mid-Southerners have named Baptist Memorial their "preferred hospital choice for quality".

The St. Jude Children's Research Hospital, leading pediatric treatment and research facility focused on children's catastrophic diseases, resides in Memphis. The institution was conceived and built by entertainer Danny Thomas in 1962 as a tribute to St. Jude Thaddeus, patron saint of impossible, hopeless, and difficult causes.

Regional One Health is located in Memphis.

Memphis is home to Delta Medical Center of Memphis, which is the only employee-owned medical facility in North America.

Individual health insurance marketplace insurers are limited, with Bright Health and Cigna offering coverage in the area.

The city's central geographic location has aided its business development. On the Mississippi River and intersected by five major freight railroads and two Interstate Highways, I-40 and I-55, Memphis is well positioned for commerce in the transportation and shipping industry. Its access by water was key to its initial development, with steamboats plying the Mississippi river. Railroad construction strengthened its connection to other markets to the east and west.

Since the second half of the 20th century, highways and interstates have played major roles as transportation corridors. A third interstate, I-69, is under construction, and a fourth, I-22, has recently been designated from the former High Priority Corridor X. River barges are unloaded onto trucks and trains. The city is home to Memphis International Airport, the world's busiest cargo airport, surpassing Hong Kong International Airport in 2021. Memphis serves as a primary hub for FedEx Express shipping.

As of 2014, Memphis was the home of three Fortune 500 companies: FedEx (no. 63), International Paper (no. 107), and AutoZone (no. 306).

Other major corporations based in Memphis include Allenberg Cotton, American Residential Services (also known as ARS/Rescue Rooter); Baker, Donelson, Bearman, Caldwell & Berkowitz; Cargill Cotton, City Gear, First Horizon National Corporation, Fred's, GTx, Lenny's Sub Shop, Mid-America Apartments, Perkins Restaurant and Bakery, ServiceMaster, True Temper Sports, Varsity Brands, and Verso Paper. Corporations with major operations based in Memphis include Gibson guitars (based in Nashville), and Smith & Nephew.

The Federal Reserve Bank of St. Louis also has a branch in Memphis.

The entertainment and film industries have discovered Memphis in recent years. Several major motion pictures, most of which were recruited and assisted by the Memphis & Shelby County Film and Television Commission, have been filmed in Memphis, including Making the Grade (1984), Elvis and Me (1988), Great Balls of Fire! (1988), Heart of Dixie (1989), Mystery Train (1989), The Silence of the Lambs (1991), Trespass (1992), The Gun in Betty Lou's Handbag (1992), The Firm (1993), The Delta (1996), The People Vs. Larry Flynt (1996), The Rainmaker (1997), Cast Away (2000), 21 Grams (2002), A Painted House (2002), Hustle & Flow (2005), Forty Shades of Blue (2005), Walk the Line (2005), Black Snake Moan (2007), Nothing But the Truth (2008), Soul Men (2008), and The Grace Card (2011). The Blind Side (2009) was set in Memphis but filmed in Atlanta. The 1992 television movie Memphis, starring Memphis native Cybill Shepherd, who also served as executive producer and writer, was also filmed in Memphis.