The crash happened in the northbound lanes just before 1:30 p.m. in Whitpain Township, Montgomery County.
Video from ABC Philadelphia affiliate WPVI showed the dark-colored SUV involved pulled off to the side of the road.
The windshield and part of the roof were caved in by the impact.
The initial word from the scene is that the tire that struck the SUV came from a truck. A pickup truck with a missing wheel could be seen stopped in the southbound lanes.
Two people were seriously injured in this crash and were flown to the hospital in medical helicopters.
"We saw fire trucks, we figured it was an accident. But once the helicopters came, it kind of felt like they were going to transport people. So it was like, okay, this is pretty bad," said Lea Agbomson of Connecticut.
She was on her way to Hershey, Pa., when she became stuck in the backlog.
"We can't really go anywhere. Pacing back and forth. Staying in the car to cool down, keeping busy one way or the other," Agbomson said.
The Northeast Extension was shut down in both directions between the Plymouth Meeting and Lansdale exits for a few hours after the crash.
Traffic was starting to get by the scene as the evening rush began.