Jackson County is located in the Appalachian foothills on the Ohio River between Parkersburg and Point Pleasant. It has 471.2 square miles of rolling, hilly land, with large flat bottoms on the Ohio River, Big Mill Creek, and Big Sandy Creek. Jackson was created from parts of Wood, Mason, and Kanawha counties by an act of the Virginia legislature, March 1, 1831. The county was named in honor of Andrew Jackson, the hero of the Battle of New Orleans and seventh president of the United States.

The first European-American to visit the area of Jackson County was probably Gabriel Arthur, a Virginian who with a party of Cherokees visited a large village of Indians that he called Monetons, now thought to have been Shawnees, in 1674. La Salle and a party of French explorers are supposed to have visited the Ohio River in the summer of 1669, but the claim cannot be substantiated. French traders were here by 1696 and their English rivals by 1703. In 1749, a party led by Celoron de Blainville and including about 200 French and Indians came down the Ohio to bury lead plates and claim the lands for France. Christopher Gist, the noted explorer, visited in 1750.

Col. George Washington, Dr. James Craik, and their party passed on their way down the Ohio River in 1770. In 1771, Capt. William Crawford made a survey of 2,448 acres for Washington in present Jackson County. The first permanent settlement was made by three Revolutionary War veterans, William Hannaman, Benjamin Cox, and James McDade, in May 1796, when they built cabins in the western part of the present county. Other early settlers were Capt. William Parsons and Samuel Tanner in 1797. Jackson was settled during the early decades of the 19th century. The first schoolhouse was erected in 1806 and the first church in 1840.

The Battle of Buffington Island, fought in Jackson County and neighboring Ohio in July 1863, ended Confederate Gen. John Hunt Morgan's daring Civil War raid north of the river. The battle on and around the island near Ravenswood involved Union gunboats and was the only naval action ever fought within West Virginia. Jackson Countians had mixed allegiances during the Civil War, provoking bitter antagonisms that persisted for many years. A period of feud-like violence in the 1870s and 1880s, known as the Bruen land wars, was traceable in part to divisions arising in the Civil War.

Jackson County's population, 4,890 in 1840, rose to more than 19,000 in 1900. The county boomed in the late 1800s, due to timbering and the oil and gas industries. The population dropped over the course of the 20th century until the 1950s, when the Kaiser Aluminum and Chemical Corporation built a large aluminum plant near Ravenswood in 1954. Unlike most of West Virginia, Jackson County's population grew each decade after 1950, peaking at 29,211 in 2010 before declining to 27,791 in 2020.

Throughout the changes, Jackson County remained farm country. It had the second-highest number of farms among West Virginia counties in 1997, and only six counties had more farmland. Jackson County farmers drew relatively little income from their farms, however, suggesting that most were part-time farmers or hobby farmers. The county includes a sizable contingent of rural gentry, some of them influential in the affairs of the state.

The Kaiser Aluminum plant, an integrated facility that included the smelting and processing of aluminum, was sold to Ravenswood Aluminum Corporation in 1988. The community was divided by a bitter strike at Ravenswood Aluminum in the early 1990s. In 1995, Ravenswood Aluminum was purchased by Century Aluminum which, in turn, sold its rolling mill to Pechiney Rolled Products in 1999. The remaining portion of the Century Aluminum plant, where aluminum was actually made, was idled in February 2009 and closed in 2015. In 2022, Berkshire Hathaway announced the purchase of 2,000 acres around the former plant with intentions of manufacturing titanium at the site in what the corporation described as "a first-of-its kind renewable energy microgrid-powered industrial site."

The rolling mill portion of the plant was acquired by Alcan in 2003 and Rio Tinto in 2007. Rio Tinto sold the division that included the rolling mill in 2011, and it is now owned by Constellium Rolled Products, the county’s biggest employer. In 2023, Jackson County's other largest employers were the county school system, Walmart, WVU Medicine, and Star Plastics.

Jackson County is served by Interstate 77 and U.S. 33, CSX Railroad, Jackson County Airport, and barge traffic on the Ohio River. The two biggest towns are Ripley and Ravenswood.

Ripley, the county seat, was laid out in 1831 by Jacob Starcher and received its charter December 19, 1832. The town was named in honor of Harry Ripley, a minister who drowned in Big Mill Creek. Ripley's role as the county seat was challenged by an 1886 referendum proposing that Ravenswood was a better choice due to its larger population and its location on the Ohio River. The referendum was defeated, ending a 54-year dispute between large landowners on the river and small inland landowners.

Ripley was the site of West Virginia's last public hanging in 1897. In 2020, Ripley's population was 3,074. Ravenswood, Jackson County's largest town with 3,865 people in 2020, was laid out in 1836 on land previously owned by George Washington.

The Cedar Lakes Conference Center, a 450-acre complex near Ripley, was established as a state FFA-FHA camp in 1950. Each summer it hosts the Mountain State Art & Craft Fair, founded as part of West Virginia's 1963 Centennial and now one of the state's largest festivals. West Virginia's American Baptist Conference Center is located just south of Ripley, on a 1,334-acre complex in Parchment Valley. In addition to serving around 700 churches, the center also is the archives for the West Virginia Baptist Historical Society. The Jackson County Maritime and Industrial Centre, a 159-acre complex located along the Ohio River, includes a 25-acre barge loading-unloading facility. The county also has Jackson General Hospital, a fine school system, public libraries in Ripley and Ravenswood, an estimated 135 churches, and local chapters of most civic and fraternal organizations.

Notable residents have included Jesse Hughes (1750-1829), a scout, frontier settler, and Indian fighter who lived and was buried here; Andrew D. Hopkins (1847-1940), an eminent horticulturist; Frederick Poe Graham (1907-82), an aviation editor, war correspondent for the New York Times, and author of books on aviation; Edithe L. Rowley (1899-74), social secretary for the White House under five presidents (1933-1964); and O. J. Morrison (1869-1952), founder of O. J. Morrison Department Stores.