The two 19 district officers were transported to the Hospital of the University of Pennsylvania where they were expected to be treated and released.
The two civilians were taken to Lankenau Medical Center for treatment.
The accident involving a police cruiser and another vehicle occurred shortly before 9:00 p.m. Monday in the southbound lanes of City and Lancaster avenues.
Initial reports say the police cruiser turned onto City Avenue and, for reasons yet to be determined, left the roadway. The cruiser then struck a tree, bounced back into traffic, and collided with the other vehicle.
Police are trying to confirm if the cruiser was actually struck first by another vehicle that did not stop.
City Avenue was closed in both directions following the crash.