Officers responded around 9:45 a.m. to a report of shots fired near West Lexington Street and South Kolmar Avenue in the Lawndale neighborhood.
Investigators said the two victims were riding in a vehicle headed east on Lexington when a black SUV pulled up alongside them and the driver opened fire.
A 21-year-old man sitting in the back and a 23-year-old man sitting in the front passenger seat were both shot in the head.
A 26-year-old man who was driving the vehicle was not hurt. He rushed the other two men to West Suburban Hospital in Oak Park, where they were listed in critical condition.
The 21-year-old man later died at the hospital. His identity has not yet been released.
The 23-year-old man's condition stabilized at West Suburban. He was transferred to Stroger Hospital. Police said he is a documented gang member.
No one is in custody. Area North detectives are investigating.
Investigators determined early Monday afternoon that a red car involved in a crash near the ramp from inbound I-290 to South Cicero Avenue was not involved in the shooting.
Police initially thought car might have been involved because the crash occurred around the time the shooting took place and near the scene. Further investigation showed the car struck a fence in an unrelated crash, police said.