The highway permits through traffic on US 59 to bypass the cities of Atchison, Kansas and Saint Joseph, Missouri, traveling instead through Falls City, Nebraska and Hiawatha, Kansas (assuming the bridge over the Missouri River is open).

The highway provides an important connection between Falls City, Nebraska and Hiawatha, Kansas, providing Nebraska residents with an alternative connection to St. Joseph, Missouri when there is a problem with the Rulo bridge.

U.S. Route 159 enters Nebraska through its southern border in Richardson County.

After the eastbound turn, U.S. Route leaves the state at the Missouri River bridge in Rulo, Nebraska.

[2] In April 2019, a large portion of this route was closed for several months because of flooding of the Missouri River.