The highway runs somewhat parallel to the Minnesota border to the east and passes through two major cities, Fargo and Grand Forks.

There are exits with no major communities near them about every eight miles (13 km) from the South Dakota state line to Fargo.

North of Fargo, with a speed limit of 75 mph (121 km/h), there are exits roughly every six miles (9.7 km) until the route enters Hillsboro.

With a speed limit of 75 mph (121 km/h), 10 miles (16 km) north of the city, I-29's first concurrency with US 81 ends in Manvel.

The highway crosses the international border at an approximate elevation of 800 feet (245 m) above sea level.

Plans for I-29 were extended from Sioux Falls to Fargo in October 1957, and the entire highway from Kansas City, Missouri, to the Canadian border was signed as I-29.