California Highway Patrol Officer Jason Gerard says three passengers were flown by helicopter and four others were taken by ambulances to hospitals.
He says 14 others were taken by bus to a hospital for evaluation of minor injuries including bumps and bruises.
The driver of the bus was unhurt.
The crash occurred around 2:15 a.m., just west of Blythe near the Arizona border.
The bus, with 32 confirmed passengers, was traveling from El Paso to Los Angeles.
All lanes of the interstate were expected to remain closed until at least Wednesday afternoon.