At one point both directions of the freeway were shut down near Nordhoff Street as authorities worked to treat patients and clear the wreckage.
The northbound lanes were later reopened, but traffic passed slowly by the debris. The southbound lanes remained closed for hours after the 1 p.m. crash.
The southbound lanes finally reopened just after 11 p.m.
Firefighters evaluated about 40 people for injuries after the crash. Of those, five were listed in critical condition, including the bus driver, and 20 were sent to the hospital with a range of minor to moderate injuries.
Authorities said the driver, identified as 60-year-old Ofelia Rodriguez of Granada Hills, suffered several broken bones.
The crash involved a private charter bus that was carrying 37 passengers back from a church event at the Forum in Inglewood. Other buses were also caravaning from the event, but were not involved in the crash.
Authorities say the bus collided with cars on the northbound side and then plowed through the center median and struck cars in the southbound lanes.
The southbound lanes were shut down for 10 hours at Nordhoff Street as the CHP worked to divert traffic from the area.
The cause of the crash is under investigation.