U.S. Route 51 (US 51) in the U.S. state of Illinois, is a main north–south artery that runs from the Ohio River north to the Wisconsin border, a distance of 415.95 miles (669.41 km).

The highway remains two lanes wide from Dongola to Assumption with the exception of a 10-mile (16 km) section between Centralia and I-64.

Over the years, it became a heavily traveled highway, often experiencing many accidents, particularly in the northern half of the state.

In addition, north of Rockford, US 51 was rerouted onto the existing I-90 segment between South Beloit and Cherry Valley.

South of Bloomington–Normal to Decatur, US 51 remained largely on the original alignment, and it was expanded to an expressway.