Incumbent Republican Jeff Fortenberry, who had represented the district since 2005, ran for re-election.

Incumbent Democrat Brad Ashford, who had represented the district since 2015, ran for re-election.

Scott Kleeb, a businessman who was the nominee for Nebraska's 3rd congressional district in 2006 and for the U.S. Senate in 2008, was speculated to challenge Ashford, a centrist Democrat, from the left.

Former state senator and Douglas County Commissioner Chip Maxwell, who considered running as an independent against Terry in 2012,[5] and retired United States Air Force brigadier general Don Bacon ran in the Republican primary.

It was mostly sparsely populated but included the cities of Grand Island, Kearney, Hastings, North Platte and Scottsbluff.