The crash occurred in foggy conditions shortly before 1 p.m. and closed northbound lanes for about three hours between the southern San Joaquin Valley and Los Angeles, creating a miles-long backup.
California Highway Patrol Officer Scott Jobinger said 11 people were injured and taken to hospitals, including four who suffered major injuries and were flown out by helicopter.
The big-rig was displaying hazardous materials placards but its unknown cargo was not compromised, Jobinger said.
The collision scene was about 1 1/2 miles long and the truck came to rest on the side of the highway near Grapevine Road, about 70 miles northwest of Los Angeles.
The truck driver reported that his brakes failed on a downhill stretch on the northern side of Tejon Pass near Lebec, Jobinger said.
Investigators will examine the brakes to determine if they were working. The fog could have also been a contributing factor, he said.
Heavy fog blanketed the southern San Joaquin Valley and spilled into the pass during the day. Visibility was reported as low as 250 feet at the time of the accident, so CHP patrol cars were pacing vehicles around the time of the accident.
The National Weather Service issued a dense fog advisory for central and southern areas of the valley between 6 p.m. Wednesday and 10 a.m. Thursday, warning that visibility could quickly drop and make driving conditions dangerous.