The crash occurred at about 10 p.m. in the 5300-block of South Dorchester Avenue.
Police said a 28-year-old motorcycle driver was going westbound when he disregarded a traffic signal and crashed into a black sedan going southbound.
The motorcycle driver was transported to the University of Chicago Medical Center, where he was pronounced dead, police said.
A 20-year-old man driving the sedan and two male passengers were hospitalized in good condition, police said.
No one is in custody and no citations have been issued.