Illinois Route 121 is a major state road in central Illinois. Although it runs from northwest to southeast, it is marked as a north–south road. It runs from Illinois Route 130 in Greenup (very near U.S. Route 40) to Interstate 55 in Lincoln at the intersection of I-55 and Illinois Route 10. This is a distance of 109.48 miles (176.19 km).

Illinois 121 runs north from Greenup near Interstate 70. While traveling northwest, Illinois 121 passes through Toledo and has an interchange with Interstate 57 at Mattoon.

From there it runs northwest into the city limits of Decatur but largely goes around downtown using 22nd Street and Pershing Road. On the northwest side of Decatur, Illinois 121 intersects with the concurrent Interstate 72 and U.S. Route 51.

Illinois 121 continues further northwest into Lincoln, where it overlaps Illinois Route 10 through Lincoln as Keokuk Street and Woodlawn Road before terminating at Interstate 55 just south of Interstate 155. Illinois 10 continues west on the same road.

SBI Route 121 formerly ran from Peoria to the Indiana state line east of Chrisman. When U.S. Route 36 was established in the late 1920s, Illinois 121 was dropped east of Decatur. In 1937, Illinois 121 replaced then Illinois Route 131 and Illinois Route 132 south of Decatur to Greenup.

In 1993, Interstate 155 north of Lincoln was completed. Illinois 121 was then dropped from this stretch of freeway.

Illinois 121 had a business route through Decatur until about 1980 along Main Street and Water Street. This was replaced by Business U.S. Route 51.