The accident happened in the 300 block of E. Washington Ave.
Lt. Ed Varso with the Escondido Police Department said a black Chrysler was headed westbound on E. Washington Ave. when it collided with a silver Toyota that was attempting to exit and make a left turn on the street.
The impact sent the Toyota with the woman and child inside, up against a fence and in a front yard.
Both victims were found unresponsive in one of the vehicles and were transported to Palomar Medical Center, where they later died.
Neighbors said the woman had just picked up her son from an after school program before the collision.
Lt. Varso said the driver and passenger of the Chrysler remained on the scene and were cooperating with investigators.
It was not immediately clear what led to the crash, although neighbors complained of speeding and vehicles parked on the side of the road hindering their views of oncoming cars.
Washington Ave. between Juniper Street and Hickory Street were closed for 4 hours during the investigation.