The crash was reported at 2:28 p.m. on the big downgrade between the upper and lower crossovers, according to the California Highway Patrol.
One person was pronounced dead at the scene and four other people - a man and three children - were taken to hospitals, Los Angeles County Fire Department Dispatch Supervisor Bernard Peters said.
The man was taken to Henry Mayo Hospital in Valencia and the children to Children's Hospital Los Angeles, CHP Officer Patrick Kimball said.
The freeway was closed in both directions for about 10 minutes to accommodate the landing of a rescue helicopter, Kimball said.
One southbound lane was closed and was expected to remain so for hours, according to the CHP, which issued a SigAlert at 2:48 p.m. Southbound traffic was backed up for miles, according to the CHP.
Shortly before the crash, county firefighters put out a small spot brush fire -- sparked by a car fire, according to the CHP -- on the northbound side of the freeway just north of Vista del Lago Road, Diaz said.
One northbound lane was closed as a result of the fire, which was reported about 2:05 p.m., according to the CHP.
A SigAlert for that side of the freeway was issued at 2:15 p.m. and cancelled about 5 p.m., the CHP reported.