The shooting happened shortly after 10:30 p.m. Friday on the northbound 14 Freeway near Vista Point.
Deputies are looking for a suspect in a red compact car.
There was no word on what may have sparked the shooting. The driver was hit but he is expected to survive.
The woman passenger was not hurt.
If you have any information about this shooting, you're urged to contact the Los Angeles County Sheriff's Department's Palmdale Station at (661) 272-2400.