It happened on the westbound lanes of the Schuylkill Expressway near the Lincoln Drive exit at 2:24 a.m. Saturday.
Officials say the bus collided with a Chevy Impala, causing it to swerve off the highway.
It then flipped onto its roof in a nearby wooded area near Fairmount Park.
A total of 17 people on the bus were injured, Pennsylvania state police say. The bus passengers were in their teens and 20s.
The injuries sustained include cuts, bruises, as well as head and neck injuries.
Police say the bus driver was speeding before the crash.
The driver of the Chevy was not injured.
Troopers have since reopened the westbound lanes.