U.S. Route 281

U.S. Route 281 is a north–south United States highway. At 1,872 miles (3,013 km) long it is the longest continuous three-digit U.S. Route.

The highway's northern terminus is at the International Peace Garden, north of Dunseith, North Dakota, at the Canadian border, where it continues as Highway 10. The route between Dunseith and the border is shared with North Dakota Highway 3. The southern terminus of US 281 is in Brownsville, Texas, just short of the Mexican border. Thus, US 281 is the only continuous three-digit US route to extend from the Canadian border to the Mexican border.

U.S. 281 is a "child" of U.S. Route 81. As a result of decommissioning portions of the parent route that have been displaced by concurrent Interstate highways, the length of U.S. 281 is 672 miles longer that of its parent.