U.S. Route 421 is a spur route of U.S. 21. It runs for 942 miles (1,515.50 km) from Michigan City, Indiana, at U.S. 20, to Fort Fisher in North Carolina. The highway goes through the cities of Indianapolis, Indiana, Lexington, Kentucky, Richmond, Kentucky, Boone, North Carolina, Winston-Salem, North Carolina, Greensboro, North Carolina and ends several miles south of Wilmington, North Carolina.
|South end:||Fort Fisher, North Carolina|
|North end:||US 20 at Michigan City, Indiana|
|Highway system||NY 104 at the Canadian border in Niagara Falls, NY||States||North Carolina, Tennessee, Virginia, Kentucky, Indiana|