ISP said troopers responded to the two-vehicle crash on southbound Interstate 55 at Wentworth Avenue around 4:30 a.m. That's near the city's Bridgeport neighborhood.
One person was pronounced dead on the scene, and another was injured and transported to a local hospital.
The roadway is closed for an investigation, and all I-55 southbound traffic is being diverted to southbound Interstate 94.
What caused the crash was not immediately clear.
Authorities did not immediately provide further information.