San Bernardino County sheriff's spokeswoman Cindy Bachman said 8-year-old Joshua Robb ran out of the gates of Grandview Elementary School's playground in Twin Peaks, near Lake Arrowhead, about 11 a.m.
School staffers went after him, but the 4-foot-6-inch boy ran into the surrounding forest and could not be found, Bachman said.
"He's rather quick and this kind of behavior where he runs off is typical," Bachman said.
Robb is "severely autistic and does not respond well to loud noises or loud voices, and unfortunately in this situation we have to have the helicopter searching for him so I'm sure that is somewhat disturbing to him but it's absolutely necessary," Bachman said.
Robb's parents said he was removed from their custody and has been living with his teacher.
"A lot of prayers, just hoping that he's safe," said the boy's father, Ron Robb. "We've got a lot of search and rescue out looking for him and I'm very thankful for that."
The boy is 60 to 75 pounds with brown hair and dark brown eyes. He was last seen wearing a tan and grey-striped collared shirt, black shorts and grey sandals.
Complicating matters, he may not respond when his name is called out by helicopters and may move away from the sound of the aircraft.
The search will continue overnight for the boy, and search and rescue teams from San Diego and Riverside will join the effort at daybreak, Bachman said.
The Associated Press contributed to this report.