Nebraska Highway 21 is a highway in central Nebraska. Its southern terminus is at Nebraska Highway 23 east of Eustis. Its northern terminus is at an intersection with Nebraska Highway 2 and Nebraska Highway 92 in Broken Bow.

Nebraska Highway 21 begins a mile east of Eustis at an intersection with Nebraska Highway 23. It goes north through farmland and meets Interstate 80 shortly before Cozad. In Cozad, it meets U.S. Highway 30 and goes on a 13-mile (21 km) concurrency eastward to Lexington. At Lexington, it turns north into rural prairie areas and meets Nebraska Highway 40 in Oconto. After passing Oconto, it turns north-northeasterly and ends in Broken Bow when it meets Nebraska Highway 2 and Nebraska Highway 92.

The original version of Nebraska Highway 21 went south from Lexington and turned east to go through Beaver City and Alma. In the 1940s, U.S. Highway 283 was created and took over the segment of the highway south of Lexington, with the Beaver City-Alma segment becoming Nebraska Highway 89. In 1960, the current route was completed, as the Cozad-Eustis segment was completed, and the highway extended along US 30.

County	Location	mi	km	Destinations	Notes
Frontier	​	0.00	0.00	N-23 – Elwood, Eustis	Southern terminus
Dawson	Cozad	12.69	20.42	I-80 – Kearney, North Platte	Exit 222 on I-80
		14.05	22.61	US 30 west (Lincoln Highway) – Gothenburg, North Platte	Southern end of US-30 concurrency
	​	22.28	35.86	L-24A south
	Lexington	27.51	44.27	US 30 east (West Pacific Avenue) – Overton, Kearney	Northern end of US-30 concurrency
Custer	Oconto	52.46	84.43	N-40 – Eddyville, Callaway
	Broken Bow	73.37	118.08	N-2 / N-92 (South E Street) – Berwyn, Merna	Northern terminus
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus

• Nebraska Roads: NE 21-40