The California Highway Patrol says a car's driver did not heed a stop sign at the intersection of Dickenson and Barstow Avenues about 5:10 pm and pulled out in front of an SUV.
The three children were in the back seat of the car. It does not appear that they were wearing seatbelts, the CHP says.
Two of the children suffered major injuries and one of those two was airlifted to the Community Regional Medical Center. The other two children were transported by ambulance.
Both drivers are uninjured.
Officers say drugs or alcohol do not appear to be factors in the crash.