It happened at 8:00 p.m. Monday at 40th and Aspen Streets in the Mantua section of Philadelphia.
Police say the driver of the Route 40 bus was confronted by a man who spat in her face then fled.
Medics were called and the driver was taken to Presbyterian Hospital for treatment.
SEPTA police are reviewing surveillance tapes to see if the suspect was recorded.
The Route 40 bus travels between 2nd and Lombard Streets in Center City and Conshohocken State and Monument Roads in Wynnefield Heights.