Police say a car rear ended a bus at 30th and Chestnut streets shortly after 7:45 p.m.
Authorities say the car went through a traffic signal and struck the bus.
The bus was a route 21 bus that runs from 69th Street in Upper Darby to Penn's Landing.
Two people, a man and a woman, were briefly trapped inside the car.
However, once crews were able to remove them, the man and woman were transported to Hahnemann Hospital and Hospital of University of Pennsylvania, respectively, for treatment.
Both are believed to be in their early 20's.
There is no word yet if either was the driver.
Three people from the bus say they were also injured. They were transported to a nearby hospital with minor injuries.