Three others were injured.
Police say one of the cars was going the wrong way in the southbound lanes at around 2:30 a.m.
The cars collided near the Broad Street ramp, killing both drivers.
They've been identified as 23-year-old Michael Ingram of Newark, Delaware and 31-year-old Shelton Mack of Philadelphia.
The highway was closed for several hours while police investigated.
