US 10 enters the state from North Dakota and heads through Moorhead parallel to Interstate 94 (I-94) and US 52 until it exits the city.

East of Mounds View, US 10 is marked mostly along Interstate Highways until Saint Paul, where the route runs concurrently with US 61 to Cottage Grove.

US 10 is a divided highway along most of its length through the state, with posted 65-mile-per-hour (105 km/h) speed limits along much of the way, except for two-lane or undivided four-lane stretches through Wadena and Motley.

[6] The four-lane divided highway section between the cities of Elk River and Anoka was constructed by 1942.

[6] The freeway section of US 10 between the city of Anoka and University Avenue (at the Coon Rapids–Blaine boundary line) was completed in the early 1970s.

[7] When I-694 and I-35E were completed in the late 1960s, US 10 was then signed concurrently with these highways east of Mounds View to the city of Saint Paul.