The collision between a teal 2014 Toyota Prius and a blue 1996 GMC Suburban happened just before 1:30 p.m. near the Smokey Bear Road exit, according to the CHP.
According to the CHP, the SUV was disabled in a lane on the freeway when the Toyota rear-ended the vehicle.
The SUV flipped over on the freeway and people were trapped inside at one point, officials said.
Two adults and four children were flown to nearby hospitals. CHP said both adults sustained critical injuries and the children suffered minor injuries.
Authorities identified the driver of the Toyota as Richard Walton Wise, of Sacramento. The driver and passenger in the Suburban were identified as 29-year-old Artima Gomez Flores and 53-year-old Lucilla Flores, both of Oxnard.
Two of the children in the Suburban were 8 years old, while the other was six. All of the children are also from Oxnard.
Traffic was backing up for miles as the southbound lanes of the 5 Freeway were closed. The lanes have since reopened.
CHP said they did not believe drugs or alcohol were a factor in the crash.