The crash was reported shortly after 9 p.m. near Las Virgenes Road, according to a California Highway Patrol log.
One of the vehicles struck the center median and rolled from the southbound side of the freeway into the northbound lanes.
Los Angeles County firefighters responded to the scene, where they extricated one victim who suffered a minor injured. Another victim was killed in the collision, but whether they died at the scene or at a hospital was unclear.
Traffic was backed up in both directions as some lanes were closed in each direction.
The cause of the crash is under investigation.