Wirt County was created by the General Assembly of Virginia, January 19, 1848, from portions of Wood and Jackson counties. It was named for William Wirt, Virginia statesman and the presidential candidate of the Anti-Masonic Party in 1832. Located in west-central West Virginia, Wirt is bounded by Wood, Ritchie, Calhoun, Roane, and Jackson counties. It comprises 235.1 square miles and had a 2020 population of 5,194, the smallest of any county in West Virginia.

Following the creation of West Virginia in 1863, Wirt County was divided into seven districts: Elizabeth, Clay, Burning Springs, Newark, Reedy, Tucker, and Spring Creek. In addition to Elizabeth, the largest town and county seat, other communities include Newark, Freeport, Morristown, Pee Wee, Creston, Munday, Brohard, and Palestine. The county courthouse at Elizabeth is a Greek Revival structure with a clock tower. It replaced the original courthouse, which burned in 1909.

Elizabeth is centrally located along the Little Kanawha River, which divides Wirt County in half. Known originally as Beauchamp's Mills, Elizabeth was chartered by the General Assembly in 1822. It was named for Elizabeth Woodyard Beauchamp, wife of David Beauchamp, who owned and operated a mill on the site. Beauchamp was the son of William Beauchamp Sr., one of the earliest settlers in the region (1799) and a notable lay minister who established the first Methodist class and organized church in the county. Other early settlers included Thomas Pribble, Isaac Enoch, Jacob Deem, Richard Lee, and William Dent at Newark; Alexander and John G. Henderson and Reuben Dye at Burning Springs; Elijah Rockhold and William Booher (who first lived in a cave) at Goose Creek; Johnathan Sheppard, John and Peter Conrad, and John Hartley at Reedy Creek; and Barney McGraw at Spring Creek, who planted the first apple orchard in the Little Kanawha Valley in 1800. The first people of European descent to explore the area, in 1772, were frontier scouts Jesse and Elias Hughes, for whom the Hughes River was named, and their brother-in-law, William Lowther.

The history of Wirt County in the 19th century is largely the history of the local oil fields. Early settlers noticed a layer of oil on the streams and discovered the famous Burning Springs, an oil and gas spring that would ignite when fired. As early as 1819, George Lemon was extracting "sand oil" from shallow pits. Bushrod W. Creel carried on a similar operation at Oil Springs Run on the Hughes River and earned a small fortune selling petroleum. Wirt County prospered as the advent of steamboats and railroads increased the demand for oil as a lubricant for steam engines.

In 1840, William P. Rathbone, a New York City judge and alderman, along with his sons, John Castelli "Cass" Rathbone and John Valleau "Val" Rathbone, purchased 12,000 acres at Burning Springs Run. They laid out the village of Burning Springs. In 1860, a Pennsylvania promoter, Samuel D. Karnes, leased an acre from the Rathbones, and drilled an oil well that within a few weeks was producing 30 barrels a day. Following his lead, Cass Rathbone sank a well on his property and hit a gusher that produced 100 barrels a day. Others rushed to Burning Springs to make their fortune, and the Rathbones, who owned most of the adjoining tracts of land, grew wealthy.

On May 9, 1863, a Confederate raiding party under Gen. William E. Jones set fire to the Burning Springs oil field and to crude oil stored in the area. The destruction of equipment and property, along with the loss of future production, was extremely costly. The discovery of new fields elsewhere in Wirt and surrounding counties moved the center of the industry to other locations. The completion of four locks and dams by the Little Kanawha Navigation Company in 1874 enabled the county's oil and gas industry to flourish in the late 19th and early 20th centuries, since producers could ship their crude oil to Parkersburg refineries more easily. Wirt County's population peaked in 1900 at 10,284. The industry's decline after 1930 spelled economic disaster for the county.

Wirt County in the 20th century was hindered by a lack of major transportation routes. No interstate highway crosses Wirt County, which is served by state and county routes. A once thriving economy has been limited, for the most part, to retailing, farming, cattle and hog raising, logging, and sawmilling. Many citizens commute to nearby Wood and Jackson counties to work.

In 2023, Wirt County's largest employers were the county school system WVUHS (WVU Home Health and Hospice) Home Care, EWV Holdings, Wirt County Health Services Association, and AJC Ventures, owner of the Food Mart in Elizabeth.

Jessica Lynch, an early heroine of the Iraq War, is among Wirt County's best known residents.