The accident happened in Merced County, near Collier Avenue in the Livingston area.
The CHP says the driver somehow lost control while heading south on 99. The car went through the median and rolled off the highway into the dry river bed.
Both people in the car were flown to a Modesto hospital in critical condition. Officers say they were both wearing seatbelts, which may have saved their lives.
Traffic was backed up for more than an hour after the crash.