U.S. Route 221 (US 221) is a 734-mile-long (1,181 km) spur of U.S. Route 21. It travels from Perry, Florida, at US 19/US 98/US 27 Alternate to Lynchburg, Virginia, at US 29 Business (Lynchburg Expressway). It travels through the states of Florida, Georgia, South Carolina, North Carolina, and Virginia. It travels through the cities of Valdosta, Georgia; Spartanburg, South Carolina; Marion, North Carolina; Roanoke, Virginia; and Lynchburg, Virginia.