Created by an act of the Virginia General Assembly, January 19, 1844, Taylor County was formed from parts of Barbour, Harrison, and Marion counties. The county was named in honor of U.S. Sen. John Taylor (1753-1824), a soldier-statesman from Caroline County, Virginia. Taylor County, served by U.S. routes 250, 50, and 119, is located in north-central West Virginia. The county has 175.6 square miles. Steep hillsides, V-shaped valleys, and narrow floodplains characterize the region.

Trapper John Simpson was the earliest person of European descent known to have entered present Taylor County, in 1768. Soon afterward, settlements were established in Booths Creek in the present county's northwestern corner.

Taylor County's early economy depended upon agriculture, timbering, and transportation. The oldest towns, including Pruntytown and Fetterman, formed along the Northwestern Turnpike, which followed the path of modern U.S. 50. Pruntytown is the oldest settlement in Taylor County, dating back to the early 1770s. The town, earlier called Cross Roads and Williamsport, was located at the junction of the Northwestern Turnpike and the Booths Ferry Pike. Fetterman also lay at a commercial junction, where the turnpike crossed the Tygart Valley River. Pruntytown served as the county seat from 1844, when Taylor County was formed, until 1878. The county seat was then moved to the railroad town of Grafton, reflecting the nation's historic move away from turnpikes and toward railroads for commerce and transportation.

The histories of the Baltimore & Ohio (B&O) Railroad, Grafton, and Taylor County are interwoven. In 1850, the Virginia legislature granted a charter to the Northwestern Virginia Railroad Company (later part of the B&O) to build a railroad from the main line of the Baltimore & Ohio to Parkersburg. A clause in the charter stipulated that the railroad should reach or cross the Tygart Valley River within three miles of Three Fork Creek, then an uninhabited area in Taylor County. Grafton, one of America's first railroad towns, emerged beside the tracks at this point in 1852. Located at the junction of the B&O main line and the branch line to Parkersburg, Grafton became an important freight and passenger hub. Today, Grafton remains an active railroad town.

Like much of West Virginia during the Civil War, Taylor County was divided in loyalty. Though most residents sided with the Grafton Guards, the local Union militia, others supported and joined the Confederate Letcher's Guard. On May 22, 1861, in a fatal encounter between these two militias, Thornsberry Bailey Brown became the first Union soldier killed in the Civil War. Control of the B&O Railroad was important for the movement of troops and supplies throughout the war. Although little military action occurred in Taylor County, there were frequent raids along the rail line, and towns in the county became hospital sites and way stations for troops. Grafton acquired a national cemetery, a federal military hospital, and a morgue. Brown is among those buried at Grafton National Cemetery.

At the beginning of the 20th century, the B&O employed about 500 men in the railroad company's repair shops in Taylor County. There were three glass factories, Tygart Valley Glass Company, Empress Glass, and the Dominion Window Glass Company. There were coal companies, including Pittsvein Coal, Wendel Coal Company, Rosemont Coal, and New York Mine. The Carr China factory in Grafton closed down in 1953, and the building was destroyed by fire in 1966.

The county's newspaper from 1870 to 1975 was the Daily Sentinel, published in Grafton. In 1975, it became the Mountain Statesman, which continues to publish three days a week.

Manufacturing, government, and public utilities are Taylor County's biggest employers today. Leading industries in the county include coal, timber, plastics, glass, horticulture, and manufactured housing. In 2023, Taylor County's largest employers were ICG Tygart Valley, the county school system, Walmart, Grafton City Hospital (Vandalia Health), and Pruntytown Correctional Center.

The region also benefits from its rugged beauty. Recreation and tourism are well established, with facilities including the Pleasant Creek Wildlife Management Area, Tygart Lake, Tygart Lake State Park, and Valley Falls State Park. The Tygart Valley River flows through the county, linking the two state parks. The U.S. Army Corps of Engineers completed the Tygart Dam in 1938 to provide flood protection for the region. The resulting 1,740-acre lake is a popular recreation area. Valley Falls State Park, once a lumber and gristmill community, is enjoyed for its waterfalls, scenic beauty, and West Virginia heritage.

Taylor County is the place where Mother's Day was first established and the birthplace of the "mother of Mother's Day," Anna M. Jarvis. Clair Bee, a championship college basketball coach and author of juvenile sports fiction, grew up in Grafton. The high school in his popular Chip Hilton books was named for Valley Falls.

Taylor County’s population peaked at 19,919 in 1940, declined to a 20th-century low of 13,878 in 1970, but had rebounded to 16,705 by 2020.