U.S. Route 421 (also U.S. Highway 421, US 421) is a diagonal northwest–southeast United States Numbered Highway in the states of North Carolina, Tennessee, Virginia, Kentucky, and Indiana. The highway runs for 941 miles (1,514 km) from Fort Fisher, North Carolina, to US 20 in Michigan City, Indiana. Along its routing, US 421 serves several cities including Wilmington, North Carolina, Greensboro, North Carolina, Bristol, Tennessee, Lexington, Kentucky, and Indianapolis, Indiana. US 421 is a spur route of US 21, which it meets west of Yadkinville, North Carolina.