The collision happened just after 1 a.m. at Frankford and Allegheny avenues in the Kensington neighborhood.
Authorities say the 23-year-old man driving a MINI Cooper was speeding down Allegheny Avenue and ran a red light.
Police say the car then crashed into the SEPTA bus, which was heading north on Frankford Avenue.
The two passengers and driver onboard the bus were not injured in the incident, officers said.
The identity of the victim has not yet been released.