It happened just before 4 am on Avenue 352 near Road 36, south of Traver.
The California Highway Patrol said the driver of a Volkswagen Jetta hit a spray rig being towed by a tractor.
The driver suffered major injuries and was transported to Kaweah Health Medical Center.
The person driving the tractor remained at the scene. It's unclear if they were injured.
Officers are working to determine what led up to the crash.