Illinois State Police said the one-car rollover crash happened near 107th Street in the city's Morgan Park neighborhood just after 7:15 p.m.
A child, who was a passenger in the car, has been pronounced dead, ISP said.
At least two other children were transported to Comer Children's Hospital, the Chicago Fire Department said.
Two adults were transported to the University of Chicago Medical Center in serious condition.
The Chicago Office of Emergency Management and Communications said I-57 inbound traffic has been condensed to one lane as officers investigate the crash.