The incident began shortly after 4 p.m. when officers responded to a report of shots fired near Valerio Street and Tujunga Avenue in North Hollywood.
Two people were hit by gunfire, one fatally, the Los Angeles Police Department said.
Officers saw two men leaving the scene and pursued them onto the busy 170 Freeway. The vehicle exited at the Burbank Boulevard offramp and stopped, police said.
"Officers surrounded the vehicle and were ordering the suspect out of the vehicle when an officer-involved shooting occurred," LAPD Det. Gus Villanueva told The Times.
It was not immediately clear whether the man was armed or brandished a weapon or whether he was killed, the LAPD said.
The second person in the vehicle was taken into custody. Investigators had not determined what sparked the initial shooting.
The California Highway Patrol said there was no estimate on when the Burbank offramp would be reopened.