It extends from Illinois Route 29 near Taylorville, west over the Illinois River at Meredosia to its western terminus in downtown Quincy.

[1] Illinois 104 crosses Interstate 55 at Exit 82 near Pawnee, and crosses Interstate 172 at Exit 14 near Quincy.

Called Broadway Street, the highway carries traffic up and down the Mississippi River bluffs that divide the city.

In Jacksonville, Illinois 104 intersects the new U.S. Route 67 Jacksonville Bypass and follows portions of the new Business U.S. 67 through the city.

Northwest of the city, Illinois 104 and U.S. 67 are concurrent for 13 miles (21 km).