It happened just after 4:30 pm Wednesday on Road 200 near Duke Road.
The California Highway Patrol says a 69-year-old woman from North Fork was driving eastbound on Road 200 when she drifted into the westbound lanes during a curve.
The woman died after she crashed head-on with a Chevy Silverado driven by a 75-year-old Fresno man.
The man suffered major injuries and was taken to Community Regional Medical Center for treatment.