It runs from the Richard I. Bong Memorial Bridge over the Saint Louis Bay at Superior, where it enters from Minnesota, east to the Michigan state line near Hurley.

US 2 then follows Belknap Street eastbound, passing through downtown Superior, where it has an intersection with Wisconsin Highway 35 (WIS 35).

After the intersection with Moccasin Mike Road, a seven-mile (11 km) freeway segment begins for US 2/US 53 as the highway leaves the city of Superior together.

[7] US 2 then continues independently again as a two-lane road, passing through Wentworth, Poplar, and Maple as it heads east to the Douglas–Bayfield county line at Brule.

US 2 then continues east, then southeast toward Hurley where it meets US 51 at its northern terminus and immediately enters Michigan,[10] continuing for 109.18 miles (175.71 km)[11] US 2 re-enters Wisconsin from Iron County, Michigan concurrently with US 141 and turns southeastward to Florence and intersects WIS 70/WIS 101 at their shared terminus.