In the state of Iowa, Interstate 74 runs south from Interstate 80 for 5.36 miles (8.63 km) before crossing into Illinois on the I-74 Bridge. North of the Mississippi River, I-74 bisects Bettendorf and Davenport.
In the state of Illinois, Interstate 74 runs south from Iowa to Galesburg; from this point it runs southeast through Peoria to the Bloomington-Normal area and Interstate 55. I-74 continues southeast to the Champaign-Urbana area, intersecting with Interstate 57. The interstate then runs east past Danville at the Illinois-Indiana state line. U.S. Route 150 parallels Interstate 74 in Illinois for its entire length, save the last few miles on the eastern end (in Danville, when US 150 turns south on Illinois 1), where it parallels U.S. Route 136.
In the state of Indiana, Interstate 74 runs east from the Illinois state line to the Crawfordsville area before turning southeast. It then runs around the city center of Indianapolis along Interstate 465. It then enters Ohio west of the city of Cincinnati, Ohio.