The accident happened on Whitesbridge Avenue in the Fresno County town of Rolinda around midnight Tuesday.
The Highway Patrol says the man was speeding when his motorcycle hit a Cadillac in front of him.
Authorities are still looking into whether alcohol played a role in the crash.
The man was taken to Community Regional Medical Center with life-threatening injuries but later died.
"He got severe injuries so there's a possibility that he may succumb to his injuries, so we're doing a thorough investigation here at the scene," Sgt. Jeremy Key of the CHP said.
A couple and a child were inside the Cadillac but were not injured. The name of the motorcycle rider has not yet been released.
