Buckhannon, the county seat of Upshur County, is located on the Buckhannon River at the juncture of U.S. 33, U.S. 119, and State Route 20. It was established in 1816 and first chartered in 1852. The population in 2020 was 5,299. Buckhannon is the home of the West Virginia Strawberry Festival and West Virginia Wesleyan College.

John and Samuel Pringle, deserters from British-American forces at Fort Pitt, settled the area in the mid-1760s. The two brothers lived in a hollow sycamore tree a few miles away from present Buckhannon. The site of the original tree has now been designated Pringle Tree Park, and a hollow sycamore tree, a natural descendant of the Pringle Tree, still stands there today.

According to one account, the Pringle brothers named the Buckhannon River after a Delaware Indian named Buckongehanon or Buckongahelas, and the town was named for the river. A statue of Buckongahelas and his son Mahonegon, erected in 2000, stands in Buckhannon’s Jawbone Park. Other historians credibly attribute the origin of the name to that of Colonel John Buchanan, an officer for Augusta County which originally included the Buckhannon River watershed and most of the rest of present West Virginia. Buchanan was of Scottish ancestry, where the surname is pronounced with a hard “k” sound, phonetically similar to the pronunciation of Buckhannon.

Buckhannon's major employers include St. Joseph's Hospital, West Virginia Wesleyan College, the Upshur County Board of Education, and Weyerhaeuser Trus Joist, a wood products manufacturer. The town has one newspaper, the Record Delta.

From 1893 to 1935, Buckhannon was home to the William Flaccus and Son tannery. From 1914 through 1939, West Virginia Wesleyan hosted the state boys' high school basketball tournament.

Buckhannon has been home to several notable people including Col. George R. Latham, a member of the U.S. House of Representatives and U.S. consul to Australia (1867-70); his daughter, artist Annie Latham Bartlett; Newbery Award-winning author Jean Lee Latham; Daniel D. T. Farnsworth, second governor of West Virginia (1869) and member of the West Virginia House of Delegates and Senate; and Laura Jackson Arnold, sister of Confederate Maj. Gen. T. J. "Stonewall" Jackson. Buckhannon is the hometown of writers Stephen Coonts and Jayne Anne Phillips. Former West Virginia Poet Laureate Irene McKinney taught at West Virginia Wesleyan.