I-80 enters Nebraska west of Bushnell. The western portion of I-80 in Nebraska runs very close to the state of Colorado, without entering the state; the intersection of Interstate 76 and I-80 is visible from the Colorado-Nebraska state line. From its intersection with I-76 to Grand Island, I-80 lies in the valley of the South Platte and Platte Rivers. The longest straight stretch of interstate anywhere in the system is the approximately 72 miles of I-80 occurring between Exit 318 in the Grand Island area and milemarker 390 near Lincoln. Along this length the road does not vary from an ideally straight line by more than a few yards. After Lincoln, I-80 turns northeast towards Omaha. It then crosses the Missouri River in Omaha to go into Iowa.
Part of Interstate 80 in Nebraska is marked as a Blue Star Memorial Highway.