After leaving US 83, it turns due east and spends about 80 miles (130 km) as a rural two-lane highway again. It overlaps US 83 for seven miles (11 km). From there, it continues east for 18 miles (29 km), until it meets with US 83 near Selby. At Walker, US 12 heads southeast for 37 miles (60 km), where it crosses the Missouri River at Mobridge, exiting the reservation. For approximately the next 70 miles (110 km), US 12 runs parallel to the border of North Dakota, sometimes within less than a mile (1.6 km). US 12 enters South Dakota from North Dakota as a rural two-lane highway about 10 miles (16 km) west/northwest of Lemmon before entering the Standing Rock Indian Reservation. US 12 meets with US 85 in Bowman, and the routes are concurrent for a short distance through the city. The speed limit is 65 mph (105 km/h) on rural segments, with slower posted speeds within the cities of Marmarth, Rhame, Bowman, Scranton, and Hettinger. US 12 is a two-lane undivided highway that runs 87.47 miles (140.77 km), through Adams, Bowman, and Slope counties in southwest North Dakota. At the east exit for Miles City, US 12 splits again from I-94 and heads almost directly east to the North Dakota border at a distance of 92.4 miles (148.7 km). US 89 splits north and US 12 continues east on its own for 233 miles (375 km), until the junction with I-94 at Forsyth as a concurrency northeast for 45.8 miles (73.7 km), to Miles City. The route joins US 89 for 8.4 miles (13.5 km) before entering White Sulphur Springs and for another three miles (4.8 km) east of town. US 12 heads east toward White Sulphur Springs for 42.2 miles (67.9 km). US 12 overlaps US 287 and heads southeast, toward Townsend for 33.4 miles (53.8 km), where it splits from US 287, which heads south for 30 miles (48 km) toward the intersection of I-90 near the town of Three Forks. US 12 passes over I-15 at which, point it joins US 287 south. 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. It then overlaps I-90 for 69 miles (111 km) until Garrison, where it heads east toward Helena for 48.8 miles (78.5 km). US 12 continues northeast through Missoula's downtown, eventually meeting I-90. After passing Lolo Peak to the south and traveling east for 33 miles (53 km), it meets with US 93 at Lolo and continues as a concurrency northeast for 7.5 miles (12.1 km), where US 93 heads due north on Reserve Street, toward Glacier National Park. The highway enters Montana at Lolo Pass, seven miles (11 km) southwest of Lolo Hot Springs in Lolo National Forest. US 12's 598 miles (962 km) through Montana's mountains and plains is the greatest distance that US 12 traverses through any state.

US 12 in Montana has been defined as the Lewis and Clark Highway despite not being the route followed by Lewis and Clark across the state. Logging truck at Lolo Hot Springs, Montana The highway's western terminus in Aberdeen is at an intersection with US 101, while the highway's eastern terminus in Downtown Detroit is at the corner of Michigan and Cass avenues, near Campus Martius Park. Highways that have been superseded by an Interstate, US 12 remains as an important link for local and regional destinations. The highway has mostly been superseded by Interstate 90 (I-90) and I-94, but, unlike most U.S. Highway 12 ( US 12) is an east–west United States Numbered Highway, running from Aberdeen, Washington, to Detroit, Michigan, for almost 2,500 miles (4,000 km). Washington, Idaho, Montana, North Dakota, South Dakota, Minnesota, Wisconsin, Illinois, Indiana, Michigan

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