Named for William H. Cabell, governor of Virginia (1805-08), Cabell County was created by an act of the Virginia General Assembly on January 2, 1809, from part of Kanawha County. Cabell County lies along the Ohio River in southwestern West Virginia, encompassing an area of 288.1 square miles and an estimated population of 94,350 in 2020. The county seat is Huntington, which is part of a metropolitan statistical area including nearby communities in Ohio and Kentucky. The city of Milton, the village of Barboursville, and other incorporated towns lie generally east of Huntington, which abuts the Ohio River.

The area was once populated by the ancient Adena people. In the early 1700s, the Shawnees, Mingos, and Senecas used present Cabell County for hunting grounds. La Salle, who navigated the Ohio River in 1669, is thought to have been the first European to set foot in the area. Thomas Hannon, who came probably in the early 1790s, is regarded as the first permanent English settler.

In 1749, the French explorer Celoron de Blainville may have landed in what is now Cabell County during his exploration of the Ohio River. Mary Ingles, who was captured and held by Shawnees in 1755 until her escape after four months, is said to have been the first woman of European descent to pass through present Cabell County. During the French and Indian War (1754-63), the Shawnees and Mingos sided with the French. During the American Revolution (1776-83), they allied themselves with the British, clashing again with settlers and discouraging further settlement of the Ohio Valley until the end of the war.

Cabell County's location along the Ohio River made it a resting point in the 1800s for settlers migrating westward. Prior to the Civil War, settlers heading west used Indian trails, including trails through the present county. On the advice of George Washington, one of these trails was upgraded to the James River & Kanawha Turnpike (modern U.S. 60), which was extended to Barboursville in 1814.

During the Civil War era, residents of Cabell County were divided in their loyalties. After the election of President Lincoln in 1860, some citizens organized the Border Rangers, a militia loyal to the South. The first engagement in Cabell County was the Battle of Barboursville on Fortification Hill in 1861, in which the 2nd Kentucky regiment of Union volunteers dispersed the local militia. Later during the war, the pro-Southern town of Guyandotte, called "the worst secession nest in that whole country" by the Wheeling Intelligencer, was set ablaze and destroyed.

Despite the damage from the war, the economy of Cabell County recovered quickly. Railroad magnate Collis P. Huntington located the western terminus of the Chesapeake & Ohio Railway just west of Guyandotte in present Huntington in 1870. The county seat was moved to Huntington by a county referendum in 1887, after being switched several times between Guyandotte and Barboursville.

By the early 1900s, industry in Cabell County included glassmaking, a flour mill, and furniture manufacturers. In 1921, the International Nickel Company plant opened. Blenko Glass, which established itself in Milton in 1921, manufactures vases and other glassware and sells stained glass throughout the world. In 1923, the Huntington area became the site of West Virginia's first commercial radio station still broadcasting today (WRVC, formerly WSAZ, which began transmitting from Pomeroy, Ohio, and moved its facilities to Huntington in 1927). In 1949, WSAZ-TV, the state's first television station, went on the air from Huntington. The completion of Interstate 64 in the 1960s, generally following the same east-west route as U.S. 60, strengthened development, though bypassing Huntington. Major sectors of the economy now include commerce, manufacturing, transportation, government, and education.

Marshall University was founded in 1837 as the Marshall Academy. It was named for the late U.S. Chief Justice John Marshall at the recommendation of his friend, Huntington lawyer John Laidley. In 1867, the new state of West Virginia created the State Normal School of Marshall College, giving Marshall a teacher-training mission. Marshall became a university in 1961 and, today, is one of the largest employers in Cabell County.

In 2023, the largest employers were the Mountain Health Network, the county school system, Marshall University, Village Caregiving, and Walmart. Historically, CSX Huntington Division had been one of the county’s leading employers, but the Jacksonville, Florida-based corporation shut down its Huntington operations in 2016. Additional economic resources include dairy and poultry farms, livestock, corn, oil wells, and coal and natural gas. Huntington is a principal trading center and shipping port for the coalfields of southern West Virginia and eastern Kentucky.

Cabell County’s population peaked at 108,202 in 1960 and, since 1990, has held relatively steady in the mid-90,000s.

Other than the Ohio River, Cabell County's major streams are the Guyandotte River and the Mud River, which flows into the Guyandotte at Barboursville. The Mud, whose banks have periodically overflowed with serious flooding of the lowlands, once was crossed by a covered bridge at Milton. This bridge, the only example of a Howe truss in West Virginia, has been moved to a pond at Pumpkin Park. The county's rivers and streams are used for boating, fishing, and swimming. Barboursville Lake north of U.S. 60 and Underwood Lake off State Route 2 are popular trout fishing sites.

The Huntington Museum of Art is a leading art gallery of the Appalachian region. Parks in the county include 70-acre Ritter Park in Huntington, Kiwanivista Park along U.S. 60 between Barboursville and Milton, and Memorial Park, dedicated to World War I veterans. Camden Park, an old-fashioned amusement park just outside Huntington, remains popular. Appropriate to the county's history as a railroad center, the annual New River Train excursion to the New River Gorge originates in Huntington and takes railroad buffs and autumn foliage observers across the state to Hinton each fall. County elected officials include three county commissioners, a county clerk, a sheriff, a prosecuting attorney, an assessor, and a circuit clerk.

In 2023, due to the county's financial struggles, the Cabell County Board of Education voted to eliminate funding for parks and libraries based on excess levies, which also are used to run the school system. The move was blocked by a circuit court decision, but in February 2024, the West Virginia Supreme of Appeals found in favor of the school board. Park and library supporters fear the cuts will cause significant budgetary problems. The first excess levy since the decision will be held in May 2024. The levy has helped fund the Cabell County Public Library since 1967 and the Greater Huntington Park and Recreation District since 1983.

The present Cabell County Courthouse was constructed on land purchased in 1895 for $24,757 and was completed December 4, 1901. An extensive remodeling and expansion were completed in 1940. Notable figures from Cabell County include Carter G. Woodson, known as the father of Black history; entertainer Soupy Sales; basketball star Hal Greer; Grammy Award winning gospel singer Michael W. Smith; Dwight Morrow, a U.S. senator (1931) from New Jersey and ambassador to Mexico; country musician Hawkshaw Hawkins; golfer Bill Campbell; cartoonist Irvin Dugan; and artists June Kilgore and Chuck Ripper.