The following highways are numbered 421:

Canada[edit]

• Manitoba Provincial Road 421
• Newfoundland and Labrador Route 421

Japan[edit]

• Japan National Route 421

United States[edit]

• 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