The man was driving alone in a 2005 Toyota Camry on northbound Highway 680 just south of Capitol Expressway when the crash happened at about 4:30 a.m.
A witness reported seeing the Camry drift to the left and strike the concrete center divider at a speed of 65 to 70 mph, CHP Sgt. Steve Oreglia said.
The Camry was only moderately damaged but the driver was pronounced dead at the scene. Oreglia said the driver may have suffered a medical problem prior to the crash.
The road's two left lanes were blocked for more than two hours. A Sig-alert was issued at 5:15 a.m. and was canceled at 6:35 a.m.