The crash was reported shortly after 9:30 a.m. at the intersection of Golden Valley Road and Centre Pointe Parkway, prompting a massive response for sheriff's deputies and firefighters.
The big rig, which was hauling gravel, was attempting to make a turn when something went awry, and it crashed into an Santa Clarita Transit bus, L.A. County sheriff's officials said. Two other vehicles were also involved in the wreck.
It's not clear what caused the crash. Sheriff's officials were working on reconstructing the crash scene as part of the investigation.
Authorities said a sobriety test was conducted on the driver of the semi, and drugs and alcohol do not appear to be a factor in the crash.
Eight people with injuries were transported to hospitals, including one individual listed to be in critical condition. Three other people were treated at the scene and released.
Emergency personnel initially said 13 people were injured in the crash but later updated that number.
Road closures were expected to be in place for several hours.