Pennsylvania State Police were called out to the east bound lanes of I-276 between the Willow Grove and Fort Washington exits around 3:30 a.m. Sunday.
According to a witness, two vehicles appeared to be racing.
Police say the vehicles lost control and crashed along the barriers at high speeds, leaving the two drivers dead.
After the initial crash, a third vehicle struck one of the crashed vehicles in the roadway.
Two occupants of the third vehicle sustained minor injuries.
A number of vehicles passing through the crash scene ran over vehicle debris causing flat tires and other damage to their vehicles.
The eastbound lanes of the Pennsylvania Turnpike between the Willow Grove and Fort Washington exits were closed for several hours Sunday morning as police investigated.
They have since reopened.