The fatal crash happened at 7 a.m. Thursday on eastbound I-580 near the North Livermore Avenue exit.
Three vehicles were involved: the semi-truck - which was not pulling a trailer - a grey Nissan SUV, and a Toyota Tundra truck, which overturned.
CHP officials say one person was killed.
Four lanes of I-580 were closed for hours after the crash.
The CHP is asking witnesses to reach out to investigators.