Authorities said the accident involving a black Chevrolet Trailblazer occurred around 6:20 a.m. near the Sierra Highway/Red Rover Mine Road exit.
For unknown reasons, the vehicle veered to the right and collided with the dirt embankment. The Trailblazer overturned several times, and a 1-year-old girl was ejected from the vehicle, the California Highway Patrol said.
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Emergency personnel were seen administering CPR to a small child who was placed into the helicopter to be taken to a hospital.
According to CHP, the 1-year-old was rushed to Antelope Valley Hospital, where she died. An 8-year-old boy also died at the hospital from injuries he sustained in the crash.
The driver, a 37-year-old woman identified as Karen Adams, and two other passengers -- another 8-year-old boy and a 14-year-old boy -- remained hospitalized with major injuries, police said.
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All northbound lanes were temporarily closed due to the wreck. Lanes began to reopen shortly before 8 a.m.
The cause of the crash was not immediately known. Police are investigating whether drugs or alcohol were involved.