For its entire distance through the state, it runs on the flat land between the Missouri River and the Loess Hills.

Between Council Bluffs and Sioux City, I-29 replaced U.S. Highway 75 (US 75) as the major route in western Iowa.

The two Interstates head west together through southern Council Bluffs for three miles (4.8 km) on separate carriageways.

North of Missouri Valley, the Interstate turns to the northwest toward Modale and then straightens out again south of Mondamin, where I-29 meets the western end of Iowa 127.

From Mondamin, it travels north for 23 miles (37 km) to the Iowa 175 interchange at Onawa, passing Little Sioux and Blencoe.

[1][3] North of Onawa, I-29 continues northwest for 15 miles (24 km) toward Sloan, where it meets the western end of Iowa 141.

At the Singing Hills Boulevard interchange, northbound is joined by southbound U.S. Highway 75 Business (US 75 Bus.).

traffic is directed onto the Interstate for 0.5 miles (0.80 km) to Exit 149, which represents the national northern end of US 77.

On April 1, 1962, some of the northbound directional spans collapsed into the Big Sioux River at the South Dakota state line as a result of flooding and bridge scour.

[12] In the mid-1980s, US 75, from Council Bluffs to Sioux City, was completely rerouted out of Iowa, instead extending up the former US 73 corridor in Nebraska.

[13] In March 2021, the Iowa DOT began a project to improve the I-29/I-480/West Broadway System Interchange at I-480's eastern terminus.