U.S. Route 54 (US 54) in Illinois is a 23.9-mile-long (38.5 km) east–west highway that travels from the Champ Clark Bridge on the Missouri state line to I-72/US 36/IL 107 south of Griggsville.

At its greatest extent, US 54 used to continue east to Springfield, then northeast to Onarga, and then north all the way to Downtown Chicago.

Beginning at the Champ Clark Bridge above the Mississippi River, US 54 travels in a northeastern direction.

In Pittsfield, one block east of Pike County Courthouse, US 54 splits northward.

That same year, the section of road that once carried Illinois Route 54 through Springfield is no longer designated as a numbered highway.