U.S. Highway 26 is an east–west highway in western Nebraska. It enters the state from Wyoming just west of Henry. The eastern terminus of U.S. Highway 26 is in Ogallala at an interchange with Interstate 80. The highway largely parallels the North Platte River for the majority of its route in Nebraska and as such, runs at a northwest-southeast angle. The highway also parallels the original paths of the Oregon Trail, the California Trail and the Mormon Pioneer Trail.

U.S. Highway 26 enters Nebraska from Wyoming, and shortly thereafter enters Henry. After passing through Morrill, US 26 becomes a divided highway. At Mitchell, US 26 meets Nebraska Highway 29. Continuing southeast, US 26 enters Scottsbluff. Through Scottsbluff, US 26 runs concurrent with Nebraska Highway 71 and Nebraska Highway 92 on a highway which goes through northern Scottsbluff. After NE 71 and NE 92 separate, US 26 continues to Minatare, Nebraska, where the divided highway ends. The highway runs due east until an intersection with Nebraska Link 62A, when the highway turns south. US 26 passes through Bayard and, after crossing the North Platte River meets with NE 92 again near Chimney Rock.

US 26 and NE 92 turn southeast towards Bridgeport. At Bridgeport, NE 92 separates and US 26 meets U.S. Highway 385. They cross the North Platte River together, and separate. US 26 continues southeasterly on the north side of the North Platte River. At Broadwater, US 26 begins its third concurrency with NE 92. They run together through Lisco, Oshkosh, and Lewellen. At Oshkosh, US 26 meets Nebraska Highway 27. At Lewellen, US 26 and NE 92 separate for the last time and shortly thereafter, US 26 crosses the North Platte River again. After passing through Ash Hollow State Historical Park, the highway passes through no communities until meeting Nebraska Highway 61 northwest of Ogallala. US 26 runs concurrent with NE 61 the rest of its length in Nebraska. The two highways go south to U.S. Route 30, then the three highways run concurrent into Ogallala. They then separate from US 30, turn south to cross the South Platte River and US 26 ends at Interstate 80.

Between 1936 and 1959, there was a U.S. Highway 26N. It went east along today's Nebraska Link 62A, then south along today's US 385 to just north of Bridgeport and east along today's US 26 to Broadwater. In those years, the mainline of US 26 between Bridgeport and Broadwater went on the south side of the North Platte River, along today's Nebraska Highway 92.

From the creation of the highway in 1926 until the 1930s, U.S. Highway 26 went north of the North Platte River east of Lewellen. This alignment went east to Martin, where US 26 met NE 61 and the two highways went south from there into Ogallala. When Lake McConaughy was built in the 1930s, the current alignment was constructed.