Police said the crash happened in the Archer Heights neighborhood's 3600-block of West 47th Street just after 1:30 a.m.
The driver of a silver sedan was heading westbound when he ran a traffic light and entered the intersection, police said. That's when the driver of a white SUV, traveling northbound, struck the sedan.
Police said the sedan's driver suffered severe trauma from the crash. The Chicago Fire Department arrived on the scene to treat the driver and transported him to Mount Sinai Hospital, where he was pronounced dead.
The drivers' ages were not immediately known.
CPD Major Accidents Unit detectives are investigating.
Police did not immediately provide further information about the crash.