The crash was reported around 6:30 p.m. Sunday in the area of Santa Susana Pass and Box Canyon roads.
The car, which had two people inside, fell more than 300 feet down the mountainside, according to the CHP.
People were trapped inside the vehicle and authorities dispatched at least two helicopters to help with the rescue. One injured patient was transported to a local hospital. The other occupant of the vehicle was pronounced dead at the scene.
Initial reports indicated two vehicles may have been involved but CHP officials later said there was only a single vehicle.
DEVELOPING: This story will be updated as more details become available.