U.S. Route 12 is a highway in west-central and east-central Minnesota, which runs from the South Dakota state line at Ortonville near Big Stone Lake and continues east to the St. Croix River at the Wisconsin state line. U.S. 12 in Minnesota is 192 miles (309 km) in length. The route connects the cities of Ortonville, Benson, Willmar, Litchfield, Minneapolis, and Saint Paul.

From the South Dakota / Minnesota state line at Ortonville, to Orono in the Twin Cities area, U.S. 12 is mostly a rural two-lane highway with a 55 MPH posted speed limit, with slower speed limits through towns and a four-lane surface arterial segment through the city of Willmar.

From Orono to Wayzata, U.S. 12 is a two-lane freeway/super-2 bypass around Long Lake.

From western Wayzata to Interstate 394 in Minnetonka, U.S. 12 is a six-lane freeway. East of Interstate 494, U.S. 12 is invisibly concurrent with Interstates 394 and 94 through Minneapolis and Saint Paul to the Minnesota / Wisconsin state line at Hudson.

U.S. 12 is invisibly concurrent with Interstate 94 in Ramsey and Washington counties.

Legally, the Minnesota section of U.S. 12 is defined as unmarked Constitutional / Legislative Routes 149, 26, and 10 in Minnesota Statutes §§ 161.115(80) and 161.114(2). U.S. 12 is not marked with these legislative numbers along the actual highway.

U.S. Highway 12 was established on November 11, 1926.

In 1929, the only sections paved were between Litchfield and Willmar; and between Wayzata through the Twin Cities to Wisconsin.

The entire route was paved by 1940.

From 2006 to 2008, the Highway 12 two-lane freeway bypass was constructed through Orono and Long Lake. The new bypass ties into the existing Highway 12 freeway at the western edge of Wayzata.