The truck was discovered in a canal bank off Highway 41, and Quebec Avenue, just north of Kettleman City, around 5 am.
Officers say the driver was traveling northbound and then crossed into the southbound lane for an unknown reason.
The truck hit the guard rail, then veered off the road. CHP officials say the vehicle rolled, ejecting the 26-year-old driver, and ended up in the canal.
The man died at the scene, officers say.
Initially, officers said there was just one victim, but after removing the truck from the water, they found a second man in his 20s dead.
Authorities say neither was wearing a seatbelt.
The California Highway Patrol says it's unclear what caused the driver to swerve into the opposite lane. The cause of the crash is under investigation.