An SUV hit the back of a semi-truck around 10:41 p.m. Thursday near the Roxford Street exit, according to a traffic log.
Two people died in the crash, according to the Los Angeles Fire Department. They have not been identified.
Video from the scene shows the SUV engulfed in flames after the collision.
2 killed in crash on 5 Freeway in Sylmar
A man who witnessed the crash described what happened after.
"I rushed over. I tried to get the semi's attention to get a fire extinguisher. By the time he could get out and use the extinguisher, the car was already engulfed. He exhausted the extinguisher and the car was still going. The fire was still going," he said.
Several lanes remained shut down into the early morning hours Friday. But all lanes were reopened to drivers by 5:30 a.m.