It happened around 6:30 p.m. Saturday in the northbound lanes of I-95 near Street Road.
Police say 19-year-old Carlee Tran of Philadelphia was driving an Oldsmobile Brovada when for unknown reason she left the roadway and traveled off to the left median of the highway.
Police say the Bravada struck the guard rail on the northbound shoulder and then went airborne.
Tran then struck a Dodge Grand Caravan being driven by 51-year-old Brian McHugh of Pennington, New Jersey.
Moments later, a Volvo being driven by Frances Jelleyman of Newtown, Pa. travelling in the middle lane of I-95 struck the Bravada.
Police say Tran's car then flipped onto its roof.
Tran and McHugh and were both pronounced dead at the scene.
Jelleyman was transported to St. Mary's Hospital in unknown condition.
Three others were also hospitalized.
The northbound lanes of I-95 reopened at 1:30 a.m.
The southbound lanes were briefly shut down after the crash.
State Police are investigating the crash to determine why the driver of the Oldsmobile lost control.