Route 280, or Highway 280, may refer to:

Australia McIvor Highway

Canada Manitoba Provincial Road 280 New Brunswick Route 280

Finland Finnish regional road 280

Japan Japan National Route 280

United States Interstate 280 (multiple highways) U.S. Route 280 Arizona State Route 280 (former) Arkansas Highway 280 Arkansas Highway 280 Spur Florida State Road 280 (former) Georgia State Route 280 Kentucky Route 280 Maryland Route 280 (former) Minnesota State Highway 280 Montana Secondary Highway 280 New York State Route 280 North Carolina Highway 280 Pennsylvania Route 280 (former) South Carolina Highway 280 Tennessee State Route 280 Texas State Highway 280 (former proposed) Texas State Highway Spur 280 Farm to Market Road 280 (Texas) Utah State Route 280