Police in Lancaster County say the crash happened shortly after 6 a.m. Saturday in the turnpike's eastbound lanes in East Cocalico Township.
Investigators said a car went out of control while negotiating a curve, crashed into a concrete barrier beneath the Route 272 overpass just south of Adamstown and rolled numerous times, ending up more than 200 feet away.
Police said 26-year-old Maria Freeman of Philadelphia and 25-year-old Rielle Hill of Philadelphia were thrown from the car and pronounced dead at the scene by the Lancaster County coroner's office.
Two other 24-year-women, at least one of whom was also from Philadelphia, were taken to Reading Hospital with severe injuries.