It travels through the Kansas City and St. Joseph metropolitan areas before exiting the state and entering Iowa.

I-29 begins at I-70 in Kansas City in a concurrency with I-35 and U.S. Route 71 (US 71) at the Downtown Loop.

I-29 and I-35 separate in northern Kansas City, with I-29 turning northwest with US 71 running concurrent with it.

I-29 then passes through rural areas of northwestern Missouri on a southeast-to-northwest alignment, then crosses into Iowa north of Rock Port, approximately 55 miles (89 km) south of Council Bluffs.

I-70 east to I-435 south was alternate a via route for traffic to void the 3 at-grade crossings.