The highway leaves the overlap near an interchange with I-35 / Downtown Loop in the downtown area, traveling along Broadway Boulevard and crosses the Missouri River via the Buck O'Neil Bridge, becoming a freeway known as the Arrowhead Trafficway.

North of Smithville, US 169 becomes a two-lane rural highway, passing through the towns of Trimble and Gower before entering St. Joseph.

North of US 136, US 169 travels through Gentry, Grant City, and Irena before exiting the state into Iowa.

On May 18, 2018, MoDOT began construction on the Buck O'Neil Bridge, with plans to repair the expansion joints, cable keep replacements and partial scour remediation.

[2] MoDOT eventually plans to completely replace the bridge, with an estimated cost of $150 million; construction would not begin until at least 2022.