The collision happened between Sacramento and Redding, west of Chico, at about 5:40 p.m. A FedEx truck was traveling southbound on I-5 when it crossed into oncoming traffic, striking a northbound Nissan Altima, then the tour bus, California Highway Patrol officials said.
Investigators said the truck may have been trying to avoid the Altima when it collided with the bus.
The drivers of the FedEx truck and the tour bus were killed. KRCR, an ABC station in Redding, reported that seven students on the bus died. Thirty-two people were hospitalized.
Los Angeles Unified School District officials confirmed at least some of the students on board attended Manual Arts High School in South Los Angeles and Robert F. Kennedy High School in Koreatown.
The total number of LAUSD students is unknown, Superintendent John Deasy said.
The uncle of one of the students told ABC7 Eyewitness News that his niece's teeth were knocked out and the family was en route to meet her.
Banning High School in Wilmington tweeted: "Our prayers go out our Banning Students who were in accident on the way to Humboldt State University and all the students in it as well."
The students were traveling north on a tour to visit the campus of Humboldt State University in Arcata.
The university released a statement: "Humboldt State University is deeply saddened by a tragic accident that occurred earlier this evening involving a charter bus filled with prospective students. They were on their way to visit campus for the April 11 Spring Preview event."