Wytheville is a town in, and the county seat of, Wythe County, Virginia, United States. It is named after George Wythe, a signer of the United States Declaration of Independence and mentor to Thomas Jefferson. Wytheville's population was 8,264 at the 2020 census. Interstate Highways 77 and 81 were constructed to intersect at the town. During the American Civil War, Wytheville had a strategic importance. It was attacked in 1863 and 1865.