It runs from Willow Hill at IL 33 north to the beginning of the U.S. Route 45/52 concurrency near Ashkum.

[1] 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.

In February 1933, the section of IL 49 from Kankakee to Chicago was designated as part of the Egyptian Highway.

[3] In 1942, U.S. Route 54 was extended to Chicago along Illinois 49 north of Kankakee.