It happened Sunday at about 8:30 pm on American Avenue near Lake Avenue, southwest of Kerman.
Officers say the 45-year-old Eliseo Vasquez veered into the opposite lane while traveling on American Avenue and collided with an oncoming Mini Cooper.
The 45-year-old woman in the Mini Cooper was airlifted to a local hospital with major injuries.
CHP officers are investigating the cause of the crash. It's unclear if drugs or alcohol were factors.