The crash, reported shortly before 12:10 p.m. on eastbound Highway 580 just east of Grove Way, involved a big-rig, a Honda and a Toyota 4Runner, CHP Officer Rob Tuazon said.
The Honda got trapped under the rear right tires of the big-rig and the lone occupant of the vehicle, a female, was killed, Tuazon said. He said it appears she was wearing a seatbelt.
The victim's identity is being withheld pending notification of next of kin by the Alameda County coroner's bureau, he said.
The driver of the 4Runner was taken to Eden Medical Center as a precaution, while the driver of the big-rig was uninjured, Tuazon said.
The crash briefly blocked all lanes of the highway, and at least two lanes were blocked for about two-and-a-half hours. All lanes were reopened shortly after 12:45 p.m., according to the CHP.
Investigators are compiling witness statements to try to determine what caused the crash, Tuazon said.