All six shooting victims were taken to hospitals, CHP spokesman Steve Loftus said. Details on their conditions were not immediately available.
The shooting took place shortly before 1:30 a.m. in the Grapevine area, on Interstate 5 near Fort Tejon Road, Loftus said.
The bus was carrying about 40 passengers.
A suspect is in custody, Loftus said. Authorities have not detailed what the motive may be.
Correction: An earlier version of this story misstated the day the shooting occurred. It happened early Monday.