Near its southern terminus, I-29 is concurrent with I-35 and U.S. Route 71. The interstate diverts from U.S. 71 just north of St. Joseph and follows a sparsely populated corridor along the Missouri River to Council Bluffs. During the design phase there was an alternative sending the route further along U.S. 71 through the bigger towns of Maryville, Missouri and Clarinda, Iowa. During the Great Flood of 1993 the Missouri River flooded this section and traffic was rerouted to U.S. 71 through Maryville and Clarinda.
Almost all of I-29 in Missouri is an area called the Platte Purchase that was not originally part of Missouri when it entered the union.
Interstate 29 begins in Iowa near Hamburg. It goes northwest to an interchange with Iowa Highway 2, then goes north until Council Bluffs. In Council Bluffs, it runs concurrent with Interstate 80. It winds its way along the western and northern edges of Council Bluffs after separating from I-80. North of Council Bluffs, I-29 runs concurrent with Interstate 680 between Exits 61 and 71. After Interstate 680 separates, I-29 continues on a northwesterly path toward Sioux City. At Sioux City, Interstate 129 spurs off of I-29 to go west toward South Sioux City, Nebraska. After continuing toward downtown Sioux City on a northerly route, it turns west and exits into South Dakota.
Interstate 29 enters South Dakota at North Sioux City by crossing over the Big Sioux River. It runs northwest until its interchange with South Dakota Highway 50 near Vermillion, where it turns north. The highway alignment is due north until just before Sioux Falls. In the Sioux Falls area, I-29 serves the western part of Sioux Falls while I-229 spurs off and serves eastern Sioux Falls. In northwestern Sioux Falls, I-29 meets Interstate 90. After that, it continues north past Brookings. At the intersection with South Dakota Highway 28, I-29 turns northwest toward Watertown. After Watertown, the highway continues north into North Dakota.
Interstate 29 enters North Dakota from the south, near Hankinson. At Fargo, it meets Interstate 94 and continues north along the Red River toward Grand Forks. At its northern terminus, I-29 enters Canada and becomes Manitoba Highway 75 which leads to Winnipeg, Manitoba.