The wreck happened around 4:00 a.m. Monday on northbound I-495, just south of the Christiana River Bridge.
Police say a jack-knifed tractor-trailer collided with a car, trapping the occupants of the car inside the vehicle.
The victims were extricated and transported to the hospital with serious, but non-life threatening injuries.
As a result of the crash, the northbound lanes of I-495 were closed between Terminal Avenue and 12th Street for a time while police conducted the investigation.
The highway has since been reopened to traffic.
The crash remains under investigation.