Two armed males entered the bus just before 1:20 p.m. in the 300-block of South Pulaski Road. They walked towards the back of the bus and opened fire, shooting two men, according to police.
The men then exited the bus and fled eastbound, police said.
A man, whose age is unknown, was shot in the head and transported to Mount Sinai Hospital in critical condition, where he was later pronounced dead.
A 24-year-old man suffered a graze wound to the head but refused medical attention at the scene, officials said.
Area Four Detectives are investigating.