Its western terminus is at the Joe Page Bridge over the Illinois River in Hardin, while its eastern terminus is at Paris at Illinois Route 1 and U.S. Route 150, with Illinois Route 133.

It runs east from Hardin to Hillsboro, and then turns northeast to Pana.

Illinois 16 then continues east to Shelbyville and then to Paris.

It overlaps Illinois 133 shortly before entering Paris.

SBI Route 16 was established in 1918, running originally from Litchfield east to Paris.