It runs in a south-to-north direction from Nebraska Highway 4 (NE-4) south of Wilcox to an intersection with Interstate 80 (I-80) in Kearney.
It heads through farmland and passes through Wilcox, then meets U.S. Route 6/U.S.
Shortly after, NE-44 crosses the Platte River and becomes a divided highway.
NE-44 then enters Kearney and meets Interstate 80, where it ends on the north side of the westbound I-80 ramps.
The roadway continues north towards downtown Kearney as Second Avenue.