All southbound lanes are shut down at Nordhoff Street due to the collision, which happened about 1 p.m., according to the California Highway Patrol.
Fire officials said a bus crash on the southbound side of the freeway caused more collisions on both sides of the freeway. Footage from AIR7 HD showed a transit bus crashed through a center divider.
A total of 40 patients were reported, 25 of which were transported by ambulance, according to the Los Angeles Fire Department. Five people are in serious condition, officials said.
The CHP said a Sigalert is in place for an unknown duration.
The cause of the crash is under investigation.