Turning west, US 275/Iowa 92 travel together for five miles (8.0 km) in Iowa and cross the new South Omaha Veterans Memorial Bridge over the Missouri River.

It continues west-northwest, meets US 20 near Inman and the two routes overlap until US 275 ends at an intersection with US 281 in downtown O'Neill.

The route followed current US 136 east from Rock Port to its intersection with US 59 near Tarkio, then south with US 59 to St. Joseph.

Before November 2001, US 275 ran alongside the Union Pacific tracks between Waterloo and Fremont, Nebraska.

This segment is officially called Reichmuth Road in Douglas County and Bell Street in Fremont.

Prior to July 1, 2003, US 275 followed a winding two-lane road between Council Bluffs and Glenwood, Iowa.

The segment moved to a concurrency with US 34 and I-29 that day as part of a mass decommissioning of highways in Iowa.

The route, which ran along a portion of West Dodge Road in Douglas County, was formerly known as US 30 Alternate (US 30A).