It happened around 8:00 p.m. Thursday at Broad and Pattison streets near Lincoln Financial Field.
Two men, ages 25 and 27, were ejected from one vehicle.
They were rushed to the Hospital of the University of Pennsylvania in critical condition.
Three others were rushed to Thomas Jefferson University Hospital in stable condition.
Police suspect alcohol played a role in the crash. One person was taken into custody.
There is no word if any of those involved were heading to the Philadelphia Eagles game.
Police are investigating.