Wilkes County is a county located in the U.S. state of North Carolina. It is a part of the state's western mountain region. As of the 2020 census the population was 65,969. Its county seat is Wilkesboro, and its largest community is North Wilkesboro. Wilkes County comprises the North Wilkesboro, NC Micropolitan Statistical Area.

Western North Carolina is the region of North Carolina which includes the Appalachian Mountains; it is often known geographically as the state's Mountain Region. It contains the highest mountains in the Eastern United States, with 125 peaks rising to over 5,000 feet in elevation. Mount Mitchell at 6,684 feet, is the highest peak of the Appalachian Mountains and mainland eastern North America. The population of the 23 most commonly associated counties for the region, as measured by the 2020 U.S. Census, is 1,149,405. The region accounts for approximately 11% of North Carolina's total population.