The California Department of Transportation said a truck carrying pipe dropped some of its load on the highway near Blythe on the Arizona border just after 2 a.m., setting off a chain reaction. The bus driver, who was headed west, apparently left the highway trying to avoid the pipe or after hitting it.
Several people were injured, some of them seriously.
The bus was owned by El Paso-Los Angeles Limousine Express Inc., and was en route from El Paso and Phoenix to Los Angeles. The company's website says it provides bus service in much of the southwest.
Terri Kasinga, a Caltrans spokeswoman, said a Chevrolet Suburban headed east struck the pipe and was heavily damaged.
Officials said the highway, the major route along the southern tier, would be shut down until at least noon.