Union Pacific spokesman Mark Davis told the Associated Press that 21 cars of a train that included 138 total cars plus three locomotives left the tracks near Fremont, Dodge County, at about 4.45am local time.
The train was traveling from Wisconsin to Wyoming, with no coal aboard.
Davis said the derailment was blocking both tracks on Tuesday and there was no timeline available as to when the tracks could be cleared.
While an investigation into the incident has only just started, officials are looking at heavy winds as a potential cause.