The crash happened around 10:19 p.m. near the Washington Boulevard exit, according to a California Highway Patrol log. At least three vehicles were involved in the collision.
Authorities said three people died at the scene, but it was not clear if the victims were in the car that caught fire or the other damaged vehicles.
Footage from AIR7 HD showed a woman on a stretcher holding a small child in pajamas. It was unclear if she and the child were severely injured or in which vehicle they were in. One other person was also injured.
A witness said he tried to help the victims after the pileup was caused by a man in a speeding Camaro who survived the incident.
"We couldn't do nothing," Omar Quintanilla said, referring to himself and two other good Samaritans. "Two of them broke the windows but the flames" were too intense.
All lanes on the southbound side were blocked for hours as authorities extinguished the flames on the car and began an investigation.
Traffic was backed up for a few miles, and vehicles were being diverted off the freeway at the nearest exit. The freeway was reopened shortly after 4 a.m. Wednesday.