Illinois Route 3 is a major north–south arterial state highway in southwestern Illinois. It has its southern terminus at Cairo Junction (about 4 miles (6.4 km), or 7 km, north of Cairo) at the intersection of Interstate 57 and U.S. Route 51, and its northern terminus in Grafton at Illinois Route 100. This is a distance of 187.44 miles (301.66 km).

Illinois 3 has 4 lanes from Waterloo to Godfrey, with a brief 6-lane stretch in Granite City around the River's Edge area (formerly the Army Depot of Granite City) and around Alton. It is 2 laned the majority of the southern part from Waterloo to Mound City around the Shawnee National Forest Area. It briefly overlaps Illinois Route 111 at Alton, Interstate 255 and U.S. Route 50, and Illinois Route 127 north of Cache.

Illinois 3 parallels the Mississippi River for the entire length of its journey, and carries the Illinois portion of the Great River Road for most of its length. South of St. Louis, Interstate 55 is its parallel on the west side of the river, along with U.S. Route 61. The road runs along many historical sites along the Mississippi River, and is the closest Illinois state highway to the old state capitol of Kaskaskia.

On August 4, 1976, the new Berm Highway from Wood River to Alton was opened. It would be signed as IL Route 3, which left the old alignment on Lewis and Clark Blvd. and Broadway unmarked. However, on June 29, 1987, IDOT built the new Madison Avenue extension in Wood River and marked that road and the Berm Highway as IL 143 and "truncated" IL 3 at IL 143 (highway signage and IDOT planning maps suggested otherwise, however). This new terminus for Route 3 was short-lived, however.

On November 26, 1987, a new section of Homer M. Adams Parkway in Alton opened to traffic, and IL 3 was extended onto Lewis and Clark Blvd. (a former IL 3 alignment) back into Alton and onto the extension. IL 3 was then cosigned with IL 111 until the intersection with Godfrey Road, where IL 3 takes over the former IL 100 alignment.

Original 1918 Route The original Illinois 3 route went from Cairo Junction in southern Illinois to Morrison in northwest Illinois via Rock Island. With the completion of highway bridges over the Mississippi River (e.g. Clark Bridge at Alton) U.S. Route 67 was extended from St. Louis to Godfrey and replacing the original Illinois 3 to Rock Island. Today, this route is still the major north–south corridor for western Illinois - and the only major Illinois north–south route never upgraded to the Interstate highway system (e.g. Interstates 57, 55, 39).