The crash happened at 6:28 p.m. at 10th Street and Avenue G.
California Highway Patrol officers said two cars collided, sending them flying off the rural desert road and into a ditch. Investigators believe some of the passengers were not wearing seat belts.
The 22-year-old woman driving the car that ran the stop sign was killed, along with a 17-year-old girl and a 17-year-old boy who were passengers in her car. The fourth person killed was a 49-year-old man riding in the other vehicle.
The names of the victims have not been released.