The following highways are numbered 281:

Canada

• Quebec Route 281

Japan

• Japan National Route 281

United States

• U.S. Route 281
• Alabama State Route 281
• Arkansas Highway 281
• California State Route 281
• Florida State Road 281
• Georgia State Route 281
• Iowa Highway 281
• Kentucky Route 281
• Maryland Route 281
• Minnesota State Highway 281 (former)
• Montana Secondary Highway 281 (former)
• New Mexico State Route 281
• New York State Route 281
• North Carolina Highway 281
• North Dakota Highway 281
• Ohio State Route 281
• Oklahoma State Highway 281A
• Oregon Route 281
• Pennsylvania Route 281
• South Carolina Highway 281
• Tennessee State Route 281
• Texas State Highway 281 (former proposed)
  • Texas State Highway Loop 281
  • Farm to Market Road 281 (Texas)
• Utah State Route 281 (former)
• Washington State Route 281