Officers say the crash was reported just before midnight on the off-ramp of Kenilworth Avenue in the northeast.
Police say a suspect in a vehicle pulled up alongside the victim while they were driving and fired shots at him. The victim crashed after the shots were fired and his vehicle overturned. The suspect, police say, fled the area.
Investigators say the victim was not struck by the gunfire but died from injuries sustained in the crash.
Southbound I-295 at Kenilworth Avenue was closed for several hours.
Investigators have not identified suspects or motives at this time.