The crash was reported at 8:20 p.m. when an Inverness man driving a 1996 Toyota Avalon drifted into the eastbound lane of Sir Francis Drake Boulevard near the intersection of Rannoch Way, and crashed into a 26-year-old Petaluma woman in a Lexus, according to the CHP.
A Marin County sheriff's deputy arrived within minutes and reported the driver of the Avalon to be nonresponsive.
Paramedics arriving at the crash at 8:40 p.m. and pronounced him dead, CHP Officer Pacheco said.
The woman driving the Lexus sustained minor injuries and was transported to Marin General Hospital.
All lanes of Sir Francis Drake Boulevard remained blocked for nearly four hours, and were cleared shortly after midnight, Pacheco said.
Preliminary reports indicate that the deceased man was not wearing a seatbelt at the time of the collision, according to the CHP.
Investigators have not determined if drugs or alcohol were factors in the cause of the crash.