It happened around 1 a.m. Wednesday at North 44th Street and Lancaster Avenue.
SEPTA police said the impact of the crash knocked the trolley off the tracks.
Firefighters worked for 15 minutes to free the driver of the car. He was taken to Penn Presbyterian Medical Center.
The operator of the trolley was also taken to the hospital suffering from neck and back pain. He is stable.
The cause of the crash is under investigation.