Authorities responded to the scene near 37th Street and Santa Fe Avenue at about 3:10 a.m., according to Vernon police.
Investigators said the driver of the 18-wheeler was involved in a minor crash near Soto and 37th streets before he ran a red light and collided with a pickup truck that was found lodged underneath the trailer of the big rig.
Authorities said the driver dragged the heavy pickup truck for several feet before stopping, jumping out and unhooking the cab from the trailer to flee the scene.
A person of interest, Guillermo Ortiz Jr., is believed to have information on the crash and authorities want to speak with him.
Two men were found trapped inside the pickup truck. Firefighters used the Jaws of Life to remove the driver from underneath the trailer and transported him to USC Medical Center in stable condition. He was expected to be OK, police said. The passenger of the truck was pronounced dead at the scene.
Several witnesses to the first crash said they followed the driver to the second location and were talking to police.
Authorities were also working to find surveillance footage that may have captured the driver or the violent scene.