California Highway Patrol officers say the crash happened in the area of Highway 33 and Douglas Ave. at about 5:48 am north of the city.
According to the CHP, one of the pick-up trucks was traveling northbound on the highway, and the other, which was towing farm equipment, was heading southbound.
As the two trucks approached one another, the one traveling northbound drifted into the other's lane and collided head-on.
Both trucks caught fire, and their drivers, who were the only occupants in the trucks, were killed.
The drivers have been identified as 34-year-old Emmanuel Espinoza of Los Banos and 21-year-old Garrett Moore of Dos Palos.