Police said officers responded to the Ashburn neighborhood's 3400-block of West 79th Street just after 10:30 p.m.
A man in his 40s was driving a black sedan westbound on 79th Street when he struck a blue hatchback, which was traveling in the same direction, police said.
Both vehicles lost control and crashed.
The sedan's driver suffered severe trauma from the crash, police said. The Chicago Fire Department treated him, but he was pronounced dead on the scene.
Police said two people were inside the hatchback, but they fled the scene before officers arrived. Whether they were injured was not immediately clear.
CPD's Major Accidents Unit is investigating.