US 12 connects the cities of Ortonville, Benson, Willmar, Litchfield, Minneapolis, and Saint Paul.

From the South Dakota state line at Ortonville, to Orono in Minneapolis–Saint Paul, US 12 is mostly a rural two-lane highway with a 60-mile-per-hour (97 km/h) posted speed limit, with slower speed limits through towns and a four-lane surface arterial segment through the city of Willmar.

From western Wayzata to Interstate 394 (I-394) in Minnetonka, US 12 is a six-lane freeway, with a posted speed limit of 65 mph (105 km/h).

East of I-494 in Minnetonka, US 12 is invisibly concurrent with I-394 and I-94 through Minneapolis and Saint Paul to the Wisconsin state line at Hudson.

[3] Beginning in the 1950s, older sections of US 12 that ran through city centers were replaced with bypasses.