From the North Dakota state line to Crookston, US 2 is a four-lane divided highway built to expressway standards for 26 miles (42 km).

This expressway portion of US 2 in northwest Minnesota passes through the cities of Mentor, Erskine, Fosston, Bagley, and the west of Bemidji.

East of Deer River, US 2 is a four-lane divided highway for seven miles (11 km) until the city of Grand Rapids, where it has a junction with US 169.

The route widens to a three-lane roadway as it approaches its intersection with Boundary Avenue (County Road 14 [CR 14]).

US 2 then exits the I-35 freeway in West Duluth and crosses the Richard I. Bong Memorial Bridge over the Saint Louis Bay, entering the state of Wisconsin and the city of Superior.

At the time it was marked, it was paved along a short concurrency with US 75 north of Crookston and from its junction with then-Trunk Highway 11 (present-day US 53) through Duluth.

In the present day, from East Grand Forks to Cass Lake, this route is built to expressway standards and a posted 65-mile-per-hour (105 km/h) speed limit.