Officials say the shooting happened around 6:35 p.m. on the westbound lanes of Highway 4 just east of Port Chicago Highway.
One victim succumbed to their injuries. Another person was struck and suffered moderate injuries.
After the shooting, officers say the victim's black Toyota crashed into a guard rail at the top of the Port Chicago offramp.
It appears there are bullet holes in the driver's side door.
The CHP shut down all westbound lanes of Highway 4 as officers gathered evidence.
A suspect vehicle left the scene, but officers have not identified a vehicle or any potential suspects.
CHP is asking anyone with information to call the CHP Investigative Tipline at 707-917-4491.