Police said it happened in the Calumet Heights neighborhood's 8800-block of South Paxton Avenue just before 8 p.m.
A 49-year-old man was driving when someone shot him in the head twice, police said. He tried to flee and crashed.
The victim was transported in critical condition to the University of Chicago Medical Center, where he was pronounced dead.
Area Two detectives are investigating. Police did not immediately provide further information.