The California Highway Patrol says the crash happened outside the city of Lindsay on Lindmore Street and Foothill Avenue just after 4 p.m. Sunday.
Investigators say a Chevy Silverado ran a stop sign at the intersection and collided with a Kia.
The collision caused both cars to roll over.
Both men inside the Kia died at the scene.
The driver of the Chevy suffered major injuries and was taken to Kaweah Health Medical Center.
The investigation is ongoing.