While approaching East 5th Street at around 55 to 60 mph, witnesses said the motorist blew through a stop sign and crashed into a van that was making a left turn.
The motorcyclist was transported to Los Robles Regional Medical Center in Thousand Oaks where he later died of his injuries.
The driver of the van was not injured.
The collision remained under investigation, and authorities did not know immediately if alcohol played a factor in the fatal crash.
The male rider was wearing a helmet at the time of the collision.