Those victims are identified as 34-year-old Karen Watts of the 7100 block of Matthias Street and 15-year-old Quinn Fleming of the same address.
The crash happened shortly after 3:00 p.m. on Kelly Drive near the Strawberry Mansion Bridge.
A Volkswagen Jetta, driven by Watts, collided head-on with a minivan. Rescue crews cut off the roof of the Jetta in attempt to rescue Watts and Fleming, but both were already dead.
The driver of the minivan, a 68-year-old woman, remains in critical condition at Hahnemann University Hospital.
Police say Watts was speeding, which may have caused the crash.
Police and eyewitnesses say it appears the Jetta swerved into the northbound lanes and hit the minivan.