The bus, carrying about 40 passengers, was headed from Los Angeles to the San Francisco area.
Shortly before 1:30 a.m., a gunman on the bus opened fire on Interstate 5, in the Grapevine area near Fort Tejon Road, CHP spokesman Steve Loftus said.
The suspect is in custody, Loftus said. CHP said the suspect boarded the bus in Los Angeles, but are not yet certain where he is from originally.
Authorities have not detailed what the motive may be.