US 12 enters South Dakota from North Dakota as a rural two lane highway about west/northwest of Lemmon before entering the Standing Rock Reservation. For approximately the next , US 12 runs parallel to the border of North Dakota, sometimes within less than a mile. At Walker, US 12 heads southeast for , where it crosses the Missouri River at Mobridge, exiting the reservation. From there it continues east for , until it meets with US 83 near Selby. It overlaps US 83 for . After leaving US 83, it turns due east and spends about as a rural two lane highway again. A few miles before reaching Aberdeen, it becomes an at-grade expressway. After the junction with U.S. Route 281, it goes back to being two lane for a few miles through Aberdeen and past the Aberdeen Regional Airport, before once again becoming a 4-lane expressway, until before Waubay. East of Waubay it becomes again an at-grade expressway until it meets with Interstate 29 near Summit. The speed limit from Aberdeen to I-29 is except through the communities of Groton, Webster and Waubay. From there it heads southeast , until Milbank. At Milbank, it continues east for 12 miles, until it crosses into Minnesota at Big Stone City, just south of Big Stone Lake. The South Dakota section of US 12 is legally defined at South Dakota Codified Laws § 31 April 132.