It travels from Niota at the Fort Madison Toll Bridge, that crosses the Mississippi River into Iowa, eastward across central Illinois to State Road 26 (SR 26) at the Indiana state line.

It crosses the Illinois River on the John T. McNaughton Bridge at Pekin, where it becomes known as Court Street in the city.

The original western terminus was in Hamilton, at the old Keokuk Rail Bridge completed in 1916 and then proceeded east through Carthage and Macomb (county seats of Hancock and McDonough counties), 9 miles (14 km) east of Macomb, southwest of New Philadelphia, the highway turned north to Bushnell and then proceeded east along the current IL 9 alignment to Canton, Peoria County, and Pekin.

The route parallels the Atchison, Topeka and Santa Fe Railway and Mississippi River to Dallas City then turns slightly southeast to LaHarpe.

From LaHarpe, the highway parallels the original Toledo, Peoria and Western Railway right-of way to Bushnell.