The bus and two other vehicles collided around 6:30 p.m. on the mountain highway north of Yucaipa and below Forest Falls, according to the San Bernardino County Fire Department.
Authorities said everyone involved in the crash sustained some kind of injury. At least 17 people were critically hurt. The injuries of those transported to hospitals ranged from life-threatening to minor.
"It's horrific, it is tragic, it is carnage," said Terri Kasinga of Caltrans. "It is so bad up there it's hard to understand what really happened."
Victims were transported to multiple area hospitals. At least three adults and two children were taken to Loma Linda University Medical Center and at least four other victims were sent to Arrowhead Regional Medical Center. Redlands Community Hospital took in two patients and two others were expected.
Investigators said there were 38 passengers and a driver in the bus, which was apparently based out of Tijuana. It was heading back from the Big Bear area. The Mexican consulate was at the scene of the crash.
Investigators said the bus rear-ended a sedan, flipped over and hit a pickup truck that was pulling a trailer. The cause of the accident was unclear, but officials said the bus driver reported having brake problems as it came down the mountain.
"Right now, we're talking to the witnesses, we're talking to the parties involved," said Officer Mario Lopez of the California Highway Patrol. "There's a possibility of mechanical issues with the bus."
The northbound SR 38 was closed while crews worked at the scene.
The Associated Press contributed to this report.