The following highways are numbered 421:
Canada Manitoba Provincial Road 421 Newfoundland and Labrador Route 421
Japan Japan National Route 421
United States U.S. Route 421 Florida State Road 421 County Road 421 (Volusia County, Florida) Georgia State Route 421 (unsigned designation for Interstate 516) New Mexico State Road 421 New York State Route 421 Ohio State Route 421 Puerto Rico Highway 421 South Carolina Highway 421 Tennessee State Route 421 Texas State Highway Spur 421