U.S. Route 81 (US 81) is a part of the U.S. Highway System that travels from Fort Worth, Texas, to the Pembina–Emerson Border Crossing near Pembina.

In the state of North Dakota, US 81 extends from the South Dakota border north to the Canada-United States border.

There it splits off to the northwest, passing through the city of Manvel.

It parallels I-29, passing by the town of Grafton before joining North Dakota Highway 5 (ND 5) near Cavalier.

The original route of US 81 survives as ND 127 and 'County Road 81' in Richland, Cass, Traill, and Grand Forks counties.