The crash was reported at about 11:40 a.m. after the gray, two-door sedan went off the road and down a cliff south of the Tom Lantos Tunnels.
Multiple CHP officers, along with other law enforcement agencies and fire crews, were dispatched to the area and closed the road while a CAL FIRE team rappelled down to check on the car's occupants, said CHP spokesman Sgt. Caleb Benefiel.
Both people in the car were pronounced dead at the scene.
The road was expected to remain closed until at least 1:30 p.m. while a tow truck crew retrieves the car from the cliffside.
Stay with ABC7 News for the latest details on this developing story.