It happened at around 11:50 pm on Monday on Highway 152 at Turner Island Road, between Los Banos and Dos Palos.
The CHP says a man, woman, and one-year-old infant were in a Kia traveling south on Turner when the driver didn't stop and drove into the path of a semi-truck headed west on Highway 152.
Both vehicles ended up in the center median.
The man and woman in the Kia, both from Dos Palos, died at the scene.
They have not yet been identified.
The baby was transported to Valley Children's Hospital with minor injuries.
The driver of the semi was okay.
One lane of Highway 152 was closed off while officers investigated the scene.