The collision Thursday evening killed both drivers, five students and three chaperones, said Lt. Bill Carpenter with the California Highway Patrol.
At least 34 people were taken to local hospitals, authorities said.
The bus was taking students from various Los Angeles-area schools to visit Humboldt State University in Arcata. The collision occurred in Orland, about 100 miles north of Sacramento.
In a statement, the university said it got word of the crash but was working to find out more details.
“Our thoughts and prayers are with everyone involved in the tragic accident on I-5 in California. We are cooperating fully with authorities as they investigate,” FedEx spokeswoman Bonnie Kourvelas said.
The truck also sideswiped another car before crashing into the bus. The condition of the car’s driver was unknown.
Tommy Chang, the instructional superintendent for the Los Angeles School District, confirmed there were local students involved. He declined to provide additional details.
“The first priority is informing parents,” he said.