It happened just after 7 a.m. near just west of Kings Canyon National Park.
Officers say the man veered off the roadway and crashed into a rock for an unknown reason. The car overturned in the westbound lane of the highway.
The man was pronounced dead at the scene. His name has not been released.
The fatal crash shut down part of the highway from Millwood Road to Highway 245 for a few hours. It has since reopened.