Throughout its 431.60-mile (694.59 km) length, the route passes through a diverse range of landscapes, including bluffs and escarpments in the Nebraska Panhandle, the Sandhills in the northern part of the state, and rolling hills and plains as the highway approaches the Missouri River valley south of Sioux City, Iowa.

These are typically two-lane highways traveling through diverse terrain and passing by historical markers and attractions that put the rich history of Nebraska's past on display.

[4] Along US-20, the route between the Wyoming state line and Valentine, a 197-mile (317 km) stretch, is designated the Bridges to Buttes Scenic Byway.

Along this route, the highway passes through diverse landscapes such as escarpments and the Sandhills as well as historical points of interest including Fort Robinson.

US-20 enters Nebraska along the Wyoming state line east of Van Tassell just north of the Niobrara River, passing through gently rolling plains with intermittent rock outcroppings on the way to Harrison.

[5] The highway then continues into the eastern reaches of Sioux County, which are marked by high plains, bluffs, and escarpments, including the Red Cloud Buttes as the road passes through Fort Robinson State Park.

To the north, the Beaver Wall escarpment provides views of the surroundings including the buttes at Crawford all the way to the Black Hills.

The route then turns southeast, running parallel to the Minnechaduza Creek along the edge of the Sandhills toward the city of Valentine.

After leaving Johnstown, the road enters flat plains where agricultural fields utilizing center pivot irrigation dot the landscape as the highway heads east toward Ainsworth.

From here, the highway continues east along the southern edge of flat plains dotted with agricultural fields into the city of O'Neill.

[3] US-20 leaves O'Neill headed southeast concurrently with US-275 for 13 miles (21 km) before turning due east toward the village of Orchard.

As US-20 continues east toward Osmond, there is a marked change in terrain as the road transitions from the flat plains to rolling hills of eastern Nebraska on the way to the Missouri River.

[2] From Osmond, the highway continues east before crossing US-81 then turns northeast and travels along with Middle Logan Creek through the communities of Randolph and Belden.

[15] This route generally followed the former Cowboy Trail, part of the Chicago and North Western Railway, from Wyoming to Sioux City via O'Neill.

[17] In November 2010, Nebraska Governor Dave Heineman approved designating US-20 from Hay Springs to Fort Robinson in honor of Crazy Horse, capping a year-long effort by citizens of Chadron.