It happened on Girard Avenue near 34th Street just before 10:30 a.m.
Chopper 6 was overhead as rescue personnel worked to aid one of the victims.
Police said a 24-year-old man was driving a white Nissan Maxima when the car hit a tree.
According to investigators, a woman was pronounced dead at the scene of the accident. A one-month-old boy and a 6-year-old girl were transported to Children's Hospital of Philadelphia.
There is no word on the extent of their injuries.