It happened near Loyola University Medical Center around 3:30 p.m. on Thursday afternoon.
Police said it appear the car crossed the center line and struck the bus. The car also struck three pedestrians in a crosswalk.
The pedestrians were taken to the hospital, two with serious injuries.
There were five passengers plus the driver on board the Pace bus. The passengers were taken to a local hospital as a precaution. The driver declined treatment.
Cook County Sheriff's Police are investigating.