The incident happened shortly before midnight in the 15300 block of Superior Street, near Plummer Street and the 405 Freeway, according to the Los Angeles Police Department.
Police say it appears the man was driving when he got into some sort of dispute with somebody. That's when officers say that person shot the driver in the back of the head, killing him.
It's unclear if the shooter knew the victim, who was only identified as a male in his 20s, and it's unclear if gang violence played any part.
Authorities closed off streets in the area as they searched for the suspect, though a description of that person was not immediately available.