[2] I-70 enters Illinois from St. Louis by crossing the Mississippi River on the four-lane Stan Musial Veterans Memorial Bridge into the village of Brooklyn in St. Clair County.

[1] Previously, I-70 ran together with I-55 and I-64 across the Poplar Street Bridge downstream, crossing into East St. Louis; when it was realigned to the current routing, the section through Downtown was absorbed into another Interstate.

I-55/I-70 curve northeast around Collinsville and leave the floodplain of the Mississippi River at the interchange with IL 157 (Bluff Road), where the highway reduces to four lanes.

The Interstate passes between Collinsville and Maryville, which are both served by the next interchange with IL 159 (Vandalia Street/Maryville Road).

The interchange, exit 20, is a full cloverleaf except for a flyover ramp for westbound I-70 to join southbound I-55.

US 40 rejoins I-70 near Pierron, and the two highways travel concurrently into Bond County, where they separate at Pocahontas.

East of Mulberry Grove, I-70/US 40 cross to the north side of the east–west rail line and again closely parallel each other into Fayette County.

I-70 crosses to the south side of both the rail line and US 40 (Cumberland Road) between Bluff City and Brownstown.

The Interstate passes to the south of St. Elmo before entering Effingham County to the west of an interchange with IL 128 at Altamont.

[1] Immediately after crossing the Little Wabash River, I-70 joins I-57 in a concurrency to pass around the west and north sides of Effingham.

In East St. Louis, I-55/I-70 extended southwest even further to directly connect to the Veterans Memorial Bridge.