It runs through the southern tier of counties in Nebraska and is always within 10 miles (16 km) of the Kansas border.

When the highway reaches Hubbell, it begins a segment where it goes northeasterly towards Fairbury until it meets N-15.

It goes north with N-15 into Fairbury, crosses the Little Blue River, then turns southeast towards Steele City.

At Pawnee City, it meets N-50 and goes east and then south with it, separating just before Du Bois.

It turns east, meets US 75 south of Dawson and ends in downtown Falls City at an intersection with US 73.