Illinois 49 runs for its length entirely as an undivided surface highway. It serves minor cities between Illinois Route 1 to the east and Interstate 57 to the west.
SBI Route 49 originally ran from Willow Hill all the way to Chicago along what is now U.S. Route 52/45 and Illinois Route 50. In 1942, U.S. Route 54 was extended to Chicago along Illinois 49 north of Kankakee. In 1969, Illinois 49 was truncated to its current northern end. When U.S. 54 was pulled back to Pittsfield in 1972, Illinois 50 took the place of Illinois 49 and U.S. 54.