Illinois Route 161 (abbreviated IL 161) is an east–west highway with its western terminus at St. Clair Avenue in Fairview Heights and its official eastern terminus at Illinois Route 37 near Kell. This is an official distance of 67.24 miles (108.21 km).

The road continues, as various county routes, eastbound beyond Illinois 37 to Allendale at Illinois Route 1.

Illinois 161 runs along portions of what once was U.S. Route 50 west of Scott Air Force Base. East of Belleville, it becomes a rural, two-lane surface road. Inside the Centralia city limits, Illinois 161 is coupled into east bound Noleman Street and west bound McCord Street.

SBI Route 161 originally ran from Belleville to Carlyle; in 1941 it was rerouted from Carlyle to Illinois 37 at its current eastern end. In 1964 it was extended west to Fairview Heights.