In the U.S. state of North Carolina U.S. Route 221 (US 221) is a north–south highway that travels through Western North Carolina. From Chesnee, South Carolina to Independence, Virginia, it connects the cities of Rutherfordton, Marion, Boone and Jefferson between the two out-of-state destinations. Its most memorable section, known as the Little Parkway Scenic Byway between Linville and Blowing Rock, offers area visitors a curvier alternative to the Blue Ridge Parkway and access to Grandfather Mountain.

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.