The CHP said that at about 7:05 a.m., officers learned about a crash in the highway's southbound lanes just north of the Mission Boulevard South off-ramp.
CHP Officer Tyler Hahn said traffic slowed down but the driver of the big-rig hauling a load of meat could not stop it in time and crashed into the rear of a Toyota Venza.
The big-rig then hit three other vehicles and went down an embankment on the right hand shoulder of the highway, Hahn said.
The Toyota driver died at the scene while two other people reported minor injuries and were taken to hospitals for treatment.
Multiple southbound I-680 lanes were shut down while authorities investigated and cleared the scene, including getting the big rig back upright. The highway reopened shortly after 1 p.m., according to the CHP.