Wilkesboro is a town in Wilkes County, North Carolina, United States. The population was 3,159 at the 2000 census. It is the county seat of Wilkes County. The town is located along the south bank of the Yadkin River, directly opposite the slightly larger town of North Wilkesboro. Wilkesboro is probably best-known as the home of the annual MerleFest festival, the largest folk and bluegrass music festival in the United States.