The lower Tennessee Valley was heavily populated with hunter-gatherers some 10,000 years ago. Their descendants, called Paleo-Indians, were succeeded by other native cultures, including the Archaic Indians, Woodland Indians, and Early Mississippians. When the first Spanish arrived in the early 16th century, Creek Indians were living in what is now East Tennessee, along with the Yuchi. About 200 years later, the powerful Cherokee—the largest single tribe south of the Ohio River, occupying parts of North Carolina, South Carolina, Georgia, and East Tennessee—drove the Creek and Yuchi out of the area and established themselves as the dominant tribe. Their settlements, varying in size from a dozen families to more than 200, were known as the Upper or Overhill Towns. The Cherokee retained their tribal dominance until they were forced out by the federal government in the 1830s. In West Tennessee, the Chickasaw were the major group. They lived principally in northern Mississippi but used Tennessee lands as a hunting ground. Shawnee occupied the Cumberland Valley in Middle Tennessee until driven north of the Ohio River by the Cherokee and Chickasaw.

Explorers and traders from continental Europe and the British Isles were in Tennessee for well over 200 years before permanent settlements were established in the 1760s. Hernando de Soto, a Spaniard, came from Florida to explore the area as early as 1540. He was followed during the 17th century by the French explorers Jacques Marquette, Louis Jolliet, and Robert Cavelier, Sieur de la Salle. Englishmen were not far behind: by the mid-1700s, hundreds—perhaps thousands—had crossed the Appalachian barrier and explored the transmontane country beyond, which was claimed first by the colony of Virginia and later assigned to North Carolina. They came in search of pelts, furs, and whatever else of value they might find. A fiercely independent breed, they were accustomed to hardship and unwilling to settle in a civilized community. Perhaps the best known was Daniel Boone, who by 1760 had found his way into present-day Washington County.

With the conclusion of the French and Indian War in 1763, many people from North Carolina and Virginia began to cross the Alleghenies. Elisha Walden was among those who first led groups of "long hunters" into the wilderness. By 1770, small pockets of white settlement were developing in the valley between the Unaka and Cumberland mountains. In the two decades that followed, more than 35,000 people settled on soil soon to become the State of Tennessee.

Two major areas of settlement developed. The larger one-in the northeast along the Holston, Nolichucky, and Watauga riverswas organized as the Watauga Association in 1791. The second major area was in the Cumberland Basin, where James Robertson, under the sponsorship of the Transylvania Company (formed by eastern land speculators), established a settlement he called Nashborough (now Nashville) in 1779. There more than 250 adult males signed the Cumberland Compact, which established a government. They pledged to abide by the will of the majority and expressed their allegiance to North Carolina.

The Revolutionary War did not reach as far west as Tennessee, but many of the frontiersmen fought in the Carolinas and Virginia. The most famous battle involving these early Tennesseans was that of Kings Mountain, in South Carolina, where Colonel John Sevier and others defeated a superior force of British soldiers and captured more than 1,000 prisoners. Hardly was the Revolution over when Tennesseans began to think about statehood for themselves. As early as 1784, leaders in three mountain counties—Greene, Sullivan, and Washington—established the Free State of Franklin. John Sevier was chosen as governor, and an assembly was formed. Only after border warfare developed and factionalism weakened their cause did Franklin's leaders abandon their plans and return their allegiance to North Carolina. But the spirit of independence—indeed, defiance—persisted.

In 1790, less than two years after Franklin collapsed, North Carolina ceded its western lands to the US. Tennessee became known as the Southwest Territory, with William Blount, a prominent North Carolina speculator and politician, as its governor. During his six-year tenure, a government was organized and a capital established at Knoxville. The population doubled to more than 70,000 in 1795, and steps were taken to convert the territory into a state. When the territorial legislature presented Congress with a petition for statehood, a lively debate ensued in the US Senate between Jeffersonian Democratic-Republicans, who urged immediate admission, and Federalists, who opposed it. The Jeffersonians triumphed, and on 1 June 1796, President George Washington signed a bill admitting Tennessee as the 16th state. Sevier became governor of the new state, Blount was elected to the US Senate, and Andrew Jackson became the state's first US representative.

Sevier dominated state politics for the first two decades of statehood, and he had little difficulty in thwarting the ambitions of Andrew Jackson and others who sought to challenge his leadership. Tennessee's population, about 85,000 when Sevier became governor, was more than 250,000 when he left the statehouse in 1809. Under Sevier's governorship, Nashville, Knoxville, and other early settlements became thriving frontier towns. Churches and schools were established, industry and agriculture developed, and Tennessee became a leading iron producer.

Andrew Jackson's rise to prominence came as a result of the Battle of New Orleans, fought at the conclusion of the War of 1812. Jackson, who had little difficulty raising troops in a state where volunteers for military service have always been abundant, lost only about a half dozen of his men, while British casualties exceeded 2,000. He returned to Nashville a hero, built a fine house that he named The Hermitage, received thousands of congratulatory messages, and conferred with friends about his political and military future. In 1823, Jackson was elected to the US Senate. Defeated the following year in a four-man race for the presidency, he ran again, this time successfully, in 1828, serving in that office for eight years.

Jackson alienated himself from many people in the state after 1835, when he announced his support of Martin Van Buren for president instead of Knoxvillian Hugh Lawson White, an avowed candidate. A majority of Tennesseans joined the new Whig Party, which arose in opposition to Jackson's Democratic Party, and voted in the 1836 presidential election for White instead of for Van Buren. The Whigs won every presidential election in Tennessee from 1836 to 1852, including the election of 1844, which sent Tennessean James Knox Polk, a Democrat, to the White House. Polk's term (1845–49) brought another war, this one with Mexico. Although Tennessee's quota was only 2,800, more than 25,000 men volunteered for service. Among the heroes of that war were William Trousdale and William B. Campbell, both of whom later were elected governor.

Social reform and cultural growth characterized the first half of the 19th century. A penitentiary was built, and the penal code made somewhat more humane. Temperance newspapers were published, temperance societies formed, and laws passed to curtail the consumption of alcoholic beverages. In 1834, a few women, embracing the feminist cause, were influential in giving the courts, rather than the legislature, the right to grant divorces. Many important schools were established, including the Nashville Female Academy, the University of Nashville, and more than two dozen colleges.

More than most other southern states, antebellum Tennessee was divided over the issue of slavery. Slaves had accompanied their owners into Tennessee in the 18th century, and by 1850, they constituted about one-fourth of the state's population. Although slaveholders lived in all sections of the state, they predominated in the west, where cotton was grown profitably, as well as in Middle Tennessee. In East Tennessee, where blacks made up less than 10% of the population, antislavery sentiment thrived. Most of those who supported emancipation urged that it be accomplished peacefully, gradually, and with compensation to the slave owners. Frances Wright, the Scottish reformer, founded the colony of Nashoba near Memphis in the 1820s as a place where freed blacks could learn self-reliance. After a few years the colony failed, however, and Wright took her colonists to Haiti. At the constitutional convention of 1834, hundreds of petitions were presented asking that the legislature be empowered to free the slaves. But while the convention endorsed several measures to democratize the constitution of 1796—abolishing property qualifications as a condition for holding office, for example—it decided against emancipation.

Considerable economic growth took place during this period. West Tennessee became a major cotton-growing area immediately after it was purchased form the Chickasaw in 1818, and Memphis, established in 1821, became the principal cotton-marketing center. The Volunteer State's annual cotton crop grew from less than 3,000 bales in 1810 to nearly 200,000 bales by midcentury. The counties of the Highland Rim produced tobacco in such abundance that, by 1840, Tennessee ranked just behind Kentucky and Virginia in total production. East Tennessee farmers practiced greater crop diversification, growing a variety of fruits and vegetables for market. Silk cultivation flourished briefly in the 1830s and 1840s.

Tennessee became a major battleground during the Civil War, as armies from both North and South crossed the state several times. Most Tennesseans favored secession. But the eastern counties remained staunchly Unionist, and many East Tennesseans crossed over into Kentucky to enlist in the Union Army. General Albert Sidney Johnston, the Confederate commander of the western theater, set up lines of defense across the northern border of the state and built forts on both the Cumberland and Tennessee rivers. In February 1862, Ft. Donelson and Ft. Henry were taken by General Ulysses S. Grant and naval Captain Andrew H. Foote, thereby opening the state to Union armies. Within two weeks Nashville was in the hands of the enemy. Northern troops pushed farther south and west, taking key positions on the Mississippi River. Less than two months later, on 6 April, Union forces near the Mississippi state line engaged Johnston's army in the Battle of Shiloh. Both sides suffered tremendous losses, including Johnston himself, who bled to death after sustaining a thigh wound. In the meantime President Abraham Lincoln had established a military government for the conquered state and appointed Andrew Johnson to head it. Johnson, who had served two terms as governor a decade earlier, had been elected to the US Senate in 1858; he remained there in 1861, the only southern senator to do so, refusing to follow his state into the Confederacy. In 1864, he was elected vice president under Lincoln.

Johnson's governorship did not mean the end of Confederate activities in Tennessee. Late in December 1862, Confederate forces made the first of two vigorous attempts to rid the state of the invader. General Braxton Bragg, who replaced Johnston as Confederate commander, established himself at Murfreesboro, 30 mi (48 km) southwest of Nashville, and threatened to retake the capital city. But at the Battle of Stones River, Union troops under General William S. Rosecrans forced Bragg to retreat to the southeast. Fighting did not resume until 19–20 September 1863, when the Confederates drove Union troops back to Chattanooga in the Battle of Chickamauga, one of the bloodiest engagements of the war. The second major Confederate drive occurred in November and December 1864, when General John B. Hood, commanding the Confederate Army of Tennessee, came out of Georgia and attacked the Union forces at Franklin and Nashville. Hood's army was destroyed, and these battles were the last major engagements in the state.

Returning to the Union in 1866, Tennessee was the only former Confederate state not to have a military government during Reconstruction. Economic readjustment was not as difficult as elsewhere in the South, and within a few years agricultural production exceeded antebellum levels. Extensive coal and iron deposits in East Tennessee attracted northern capital, and by the early 1880s, flour, woolen, and paper mills were established in all the urban areas. By the late 1890s, Memphis was a leading cotton market and the nation's foremost producer of cottonseed oil. Politically, the Democratic Party became firmly entrenched, and would remain so until the 1950s.

As the 20th century dawned, the major issue in Tennessee was the crusade against alcohol, a movement with deep roots in the 19th century. Though the major cities still were "wet," earlier legislation had dried up the rural areas and small towns, and the Tennessee Anti-Saloon League and Women's Christian Temperance Union (WCTU) kept the matter in the public eye. In 1908, with "wet" forces controlling the state government, Edward Ward Carmack—a rabid prohibitionist, powerful politician, newspaper editor, and former US senator—was shot and killed in the street of Nashville. His assailants were convicted but pardoned immediately by the governor. In the following year, with Carmack as a martyr to their cause, "dry" forces enacted legislation that, in effect, imposed prohibition on the entire state. The dominant Democratic Party was divided and demoralized to such an extent that a Republican governor was elected-only the second since Reconstruction. The prohibition movement helped promote the cause of women's suffrage. A proposed state constitutional amendment giving women the right to vote failed in 1915, but in 1919, they were granted the franchise in municipal elections. One year later, Tennessee became the 36th state to ratify the 19th Amendment to the US Constitution, thereby granting women the right to vote nationwide.

The 1920s brought a resurgence of religious fundamentalism. When, in 1925, the legislature enacted a measure that prohibited the teaching of the theory of evolution in the public schools, a high school teacher named John T. Scopes decided to challenge the law. Three-time presidential candidate and fundamentalist spokesman William Jennings Bryan arrived in the tiny town of Dayton to aid in Scopes's prosecution, while the great civil liberties lawyer Clarence Darrow came from Chicago to lead the defense. The Scopes trial gave the Volunteer State unwanted notoriety throughout the civilized world. Scopes was convicted, and it was not until 1967 that the law was repealed.

The 1930s brought depression, but they also brought the Tennessee Valley Authority. Before TVA, residents of the Tennessee River Valley could boast of the beauty of the landscape, but of little else. The soil was so thin that little other than subsistence agriculture was possible, and many people lived on cash incomes of less than $100 a year. There were some senators, such as George Norris of Nebraska and Tennessee's own Kenneth D. McKellar, who saw great possibilities in valley development. Harnessing the Tennessee River with dams could not only generate electricity inexpensively but also greatly improve navigation; aid flood control, soil conservation, and reforestation; and produce nitrate fertilizer. Efforts to establish such a program failed, however, until Franklin D. Roosevelt included it in his New Deal. The law establishing the TVA was passed a few weeks after Roosevelt's inauguration in 1933, and dam construction began almost immediately. Before TVA, people in the valley consumed only 1.5 billion kWh of electricity annually; but consumption increased to 11.5 billion kWh by 1945 and to 57.5 billion kWh by 1960. Fewer than 2% of rural families in Tennessee had electricity in 1933; but by the late 1930s, power lines were being strung into remote areas, bringing to practically everyone the advantages that hitherto only urban residents had enjoyed. Inexpensive power became a magnet for industry, and industrial employment in the region nearly doubled in two decades. The building of a plant for the production of atomic weapons at Oak Ridge in 1942 was due in large measure to the availability of TVA power.

The TVA notwithstanding, the depression caused many manufacturers to close or curtail operations, and farm prices declined drastically. Cotton, which had earlier brought farmers more than 30 cents a pound, declined to 5.7 cents, and the prices of corn, tobacco, and other crops fell proportionately. The state still was in the grip of financial depression when World War II began. Thousands of men volunteered for service before conscription was introduced; when the US entered the war in 1941, several training posts were established in Tennessee. Tennessee firms manufacturing war materiel received contracts amounting to $1.25 billion and employed more than 200,000 people during the war. Industrial growth continued during the postwar period, while agriculture recovered and diversified. The chemical industry, spurred by high demand during and after World War II, became a leading sector, along with textiles, apparel, and food processing. Cotton and tobacco continued to be major crops, but by the early 1970s, soybeans had taken the lead, accounting for 22% of estimated farm income in 1980. Beef and dairy production also flourished.

Democratic boss Edward H. Crump, who ran an efficient political machine in Memphis, dominated state politics for most of the period between 1910 and the early 1950s, an era that saw the elevation of many Tennessee Democrats to national prominence. Considerable progress was made toward ending racial discrimination during the postwar years, although the desegregation of public schools was accomplished only after outbursts of violence at Clinton, Nashville, and Memphis. The killing of civil rights leader Martin Luther King, Jr., in Memphis in 1968 resulted in rioting by blacks in that city. The most notable political development during the 1970s was the resurgence of the Republican Party, making Tennessee one of the few true two-party states in the South.

The early 1980s saw the exposure of corruption in high places: former governor Ray Blanton and several aides were convicted for conspiracy to sell liquor licenses, and banker and former gubernatorial candidate Jacob F. "Jake" Butcher was convicted for fraud in the aftermath of the collapse of his banking empire. On the brighter side, there was a successful World's Fair in 1982, the Knoxville International Energy Exposition, and a fairly resilient state economy, bolstered by the much-heralded openings of the Nissan truck-assembly plant in Smyrna in 1983 and the General Motors Saturn plant in Spring Hill in 1990.

Manufacturing in Tennessee continued to grow throughout the 1980s, aided by the completion of the Tennessee-Tombigbee Waterway in 1985. The state gained nearly 45,000 manufacturing jobs between 1982 and 1992, many of them in the automotive and other transport-related industries. Tennessee's unemployment rate fell to a 16-year low of 4.7% in 1994.

The state legislature passed school reform laws in 1992 and, in 1993, a healthcare package mandating the creation of TennCare, an insurance program designed to replace Medicaid coverage for 1.5 million uninsured residents of the state.

Democratic Governor Phil Bredesen, elected in 2002, served two terms as Nashville mayor and hoped in 2003, despite the state's budget problems, to repeat statewide the significant economic growth he spearheaded in Nashville. The state was a leader in the nation in attempting to collect internet and mail-order sales taxes. Tennessee officials estimated the state could lose up to $300 million in uncollected internet and mail-order sales taxes in 2003.