Illinois Route 99 is a north–south state road in western Illinois. It runs from Illinois Route 104 across the Illinois River and Meredosia, north to Illinois Route 101 in Brooklyn (Schuyler County). This is a distance of 32.08 miles (51.63 km).

Illinois 99 runs northwest from Meredosia to Mount Sterling. It enters the Mount Sterling area on Pittsfield Road north of Illinois Route 107. It then overlaps U.S. Route 24 and runs west on Main Street. After about a half mile (.8 km), Illinois 99 then turns north on Cross Street, west on Washington Street, and then back north on Camden Road en route to Camden and Brooklyn.

SBI Route 99 had been a route from West Point to Tennessee on local roads, Illinois Route 91, Illinois Route 61 and U.S. Route 136. In 1935 Illinois 99 was dropped from those routes. The next year, it replaced Illinois Route 104 on its current route; in 1941, Illinois 99 was extended north to Brooklyn.