After passing Lolo Peak to the south and traveling east for 33 miles (53 km), it meets with US 93 at Lolo and continues running concurrently northeast for 7.5 miles (12.1 km), where US 93 heads due north on Reserve Street, toward Kalispell and Glacier National Park.

US 12 continues northeasterly through Missoula's downtown, eventually meeting Interstate 90 (I-90).

This two-lane section of the trip passes through Avon and Elliston winding through Helena National Forest, over the Continental Divide at MacDonald Pass, and then through Montana's capital city, Helena.

On the east end of Helena, US 12 passes over I-15 at which point it joins US 287 south.

US 12 heads eastward toward White Sulphur Springs for 42.2 miles (67.9 km); the route joins US 89 (which heads south toward Livingston and Yellowstone National Park) for 8.4 miles (13.5 km) before entering White Sulphur Springs and for another three miles (4.8 km) east of town.