Kanawha County, named for the Kanawha River which flows through it, was created November 14, 1788. Initially 10 times its present size, the county remains West Virginia's fourth largest, at 908.4 square miles. Its population, the state's largest, was 180,745 in 2020, down from its 1960 peak of 252,925. The terrain ranges from the rolling hills of Teays Valley in the west to the 2,600-foot mountains on its southern border. Charleston, the capital of West Virginia and the state's largest city, is the county seat.

Kanawha County has a rich prehistory going back to at least 10,500 B.C. More than 500 archeological sites have been recorded, including St. Albans, one of the most significant Early Archaic sites in the eastern United States. People of the Adena and Hopewell cultures occupied the region at the time of ancient Rome and left behind numerous structures, including the second-largest mound in the state at South Charleston. No Indians seem to have lived in the county in the historic era, but they often passed through.

The earliest European to visit the area was probably Gabriel Arthur, as a captive of the Indians in 1674. Then came John Peter Salling and John Howard, Coal River explorers in 1742, and the captive Mary Draper Ingles in 1755. By 1771, Simon Kenton was hunting and trapping in the valley; Walter Kelly, though killed within a year, is credited with the first settlement in 1773, at Cedar Grove at the mouth of Kellys Creek. William Morris and others followed in 1774 and later, especially after Dunmore's War temporarily reduced Indian opposition. Charleston was settled in 1788 by George Clendenin.

The salt industry stimulated early economic development. Beginning with Elisha Brooks's 1797 furnace on land leased from Joseph Ruffner at the mouth of Campbells Creek, near present Malden, the industry blossomed to 52 furnaces producing 3,000 bushels of Kanawha "red salt" per day by 1815, and three times that by the late 1840s. Coal was mined to fuel the salt works by 1817, and cannel coal production boomed in the late 1840s at locations as diverse as Coal River, Mill Creek, and Cannelton. Further, sluice dams and dredging in the 1820s that allowed steamboat traffic, the 1829 authorization to complete the James River & Kanawha Turnpike to the Ohio River, and the long-awaited 1832 chartering of a Bank of Virginia branch stimulated growth. Malden was the early industrial center, but by 1830, Charleston had emerged as a respectable town of 750 people as salt magnates moved away from Malden's grime. The combination of salt workers, household servants, and laborers in Charleston, and agricultural laborers on plantations that lined the flood plain, gave the Kanawha Valley a high concentration of Black workers, most of whom were enslaved.

Given its commercial bent, the county generally supported Whig political candidates, such as Lewis Summers and George W. Summers, for their economic development views, and found itself in opposition to the Democrats who dominated Virginia east of the mountains. A number of prominent Kanawha Countians, including George Summers, Spicer Patrick, and James H. Brown, opposed Virginia secession. Nevertheless, the county was split by the Civil War. A number of Confederate companies, most notably George S. Patton's Kanawha Riflemen, were mustered in the valley. Union troops from Ohio and Kentucky under Brig. Gen. Jacob Cox occupied the valley in July 1861 only to be driven out for six weeks in the fall of 1862 by a Confederate advance led by Brig. Gen. William W. Loring. Thereafter, Charleston and the valley remained in Union hands for the duration of the war. However, much damage had been inflicted by retreating armies and by one of the valley's worst floods on September 29, 1861. The Kanawha River reached 46.87 feet in Charleston, more than 16 feet above flood stage.

After the Civil War, Kanawha County participated fully in West Virginia's transformation from a traditional economy to extractive industry and then to industrial production. Timber and particularly coal production were stimulated by the railroads. The Chesapeake & Ohio arrived in 1873, following the south side of the Kanawha River. Charleston passengers had to take a ferry trip to the depot until the first South Side Bridge was erected in 1891. The north side of the river became the province of the Kanawha & Michigan Railroad (later part of the New York Central) in the 1880s and 1890s. Traffic north along the Elk River was consolidated into the Coal & Coke Railway by 1906. Between 1875 and 1898, ten locks and dams provided year-round navigation on the Kanawha. Several branch railroads opened numerous coal camps and made the county the state's second largest coal producer by 1888.

Another stimulus for county development came from state government. The capital was moved from Wheeling to Charleston in 1870, back to Wheeling in 1875, then permanently to Charleston in 1885. The famous fire of 1921 caused the capitol building to be relocated from downtown to its present east end site by 1932.

World War I initiated the modern transformation of the county. Attracted by abundant water, salt brines, coal, gas, and petroleum, the government built the explosives plant at Nitro and ordnance facilities in South Charleston, while small chemical firms located in the valley. From these beginnings, further stimulated by World War II, large chemical complexes were developed by DuPont at Belle, FMC in South Charleston, Monsanto in Nitro, and Union Carbide, first in Clendenin, then at its large production and research facilities in South Charleston and Institute. Kelly Axe had brought additional diversity to the valley in 1904, while small glass producers paved the way for Libbey-Owens-Ford to build its large plate glass plant in Kanawha City in 1916. New locks updated river transportation in the 1930s, and air travel, initiated at Wertz Field in Institute, received modern facilities at Kanawha (now Yeager) Airport in 1947.

Kanawha County has been the center of some of West Virginia's most turbulent events. Bloody coal strikes at Cabin Creek and Paint Creek focused national attention on the mining industry in 1912-13, and the county served as a staging area for the 1920-21 union organizing confrontations at Matewan and Blair Mountain. Controversy flared over school textbooks in 1974, and numerous groups have converged on state government with their concerns.

In addition, Charleston has become the state's banking center on foundations laid by Kanawha Valley Bank, 1867, Charleston National Bank, 1884, and several others by 1910. Lawyers, particularly the so-called Kanawha Ring at the turn of the century, have wielded much power, and most West Virginia lawyers practice here. The 1972 merger of five hospitals into Charleston Area Medical Center (CAMC) created a premier medical center. Higher education stretches back to the West Virginia Colored Institute (now West Virginia State University), 1892, and the Montgomery Preparatory School (now West Virginia University Institute of Technology), 1895. Morris Harvey College (now University of Charleston) moved from Barboursville to Charleston in 1935. Finally, with its French and Belgian glass workers, Italian and Irish stone masons, Welsh, Polish, Hungarian, and African-American miners, Jewish, Greek, German, and Lebanese merchants, Asian chemists and doctors, Kanawha County has contributed to the ethnic diversity of the state.

A deadly flood on the Elk River in 2016 devastated communities in the northeastern part of the county, particularly Clendenin and Elkview.

In 2023, Kanawha County's largest employers were Vandalia Health (CAMC), the county school system, WVU Medicine, the state Department of Health and Human Resources, and the state Division of Highways.

Notable individuals who have resided in the county include frontiersman Daniel Boone; educators Henry Ruffner and Booker T. Washington; Civil War Gen. William S. Rosecrans; naturalist William H. Edwards; presidential assassin Leon Czolgosz and attempted assassin Sara Jane Moore; entrepreneurs Alex Schoenbaum and Fred Haddad; union presidents Arnold Miller and Cecil Roberts; League of Women Voters president Becky Cain; civil rights activist Leon Sullivan; journalist Tony Brown; composer George Crumb; writers Denise Giardina, Mary Lee Settle, and Eugenia Price; and athletes Jerry West, Rod Hundley, Dennis Harrah, and Randy Moss. Kanawha County has produced 11 members of the U.S. Congress, seven members of the U.S. Senate, and six governors of West Virginia.