Officials said the driver and two students were critically injured in the crash and that three other students had minor injuries.
CHP spokesman Officer Florentino Olivera said a full investigation would be conducted. But he added that preliminary evidence indicates that the brakes may not have been used prior to the crash along East Nohl Ranch Road by the Anaheim Hills Golf Course.
"I don't see any skid marks. It looks like he went straight into the tree," Olivera said.
The injuries to the two students did not appear to be life-threatening, fire officials said. The six remaining students were released at the scene to family or friends, Olivera said. "They might have had scratches or bruises," he said.
As the driver moved along East Nohl Ranch Road, the yellow bus suddenly picked up speed, according to student Solymar Colling, 14, who was sitting in the third row.
"It started going up fast, we went up and then it hit the tree," Colling said. "People were screaming."
She said she flew into the seat across from her as the bus crashed into the tree.
"I started looking for my phone," she said, "so I could call 911 and say we need to get off the bus."
Tyler Fabozzi, 17, and a senior at Canyon High School, was driving next to the bus when it swerved into his lane and suddenly swerved back.
Fabozzi continued to drive alongside the bus when it suddenly drove up the grassy hill and knocked down a tree.
Fabozzi parked his truck and ran up the hill to help the students. He found the fuel door near the emergency hatch and turned off the gas line, he said.
Colling said she and the other students were inside the bus for about a minute or two before they started to make their way to the back where someone had opened an emergency exit. The vehicle was clouded with dust and debris from the smashed tree.
Among those who helped the students as they exited the bus was Ahaheim Hills resident Claudia Matten. She recalled hearing a loud crack as she walked along the roadway and saw the bus come to a stop amid the trees as students were screaming.
"They were crying, saying, 'I'm hurt. Help me!" Matten said.
Some of the students had scrapes and bruises on their heads, Matten said. Others complained of neck pain.
She said that one girl's toes were scraped and bleeding. A boy was stuck in the bus and had to removed by a man who rushed inside and carried him out.
The driver had to be rescued from the bus by firefighters, who pulled the man out from the front end of the vehicle. He has been a full-time driver with the Orange Unified School District since October 2010, officials said. His name and age were not released.
Ellen Johnson, transportation supervisor for the Orange Unified School District, said the bus was equipped with seat belts and that students "are directed by the bus driver to put them on."
Olivera of the CHP said his agency conducted a safety inspection of the bus in October and that it "passed with flying colors."
He said investigators would examine the bus to make sure "everything was working the way is was supposed to."
Olivera said investigators were also planning to interview the bus driver, perhaps as early at Thursday night in the hospital.