The crash was reported at about 8:05 a.m. in the 4200 block of Middlefield Road, just south of San Antonio Road.
Police said it appears the man was driving north on Middlefield Road when his car crossed into southbound lanes, went onto the sidewalk and struck a tree.
The driver, who was alone in the car, was pronounced dead at the scene. His name has not yet been released.
No other cars were involved and no one else was injured. Investigators believe it is possible the victim suffered a medical emergency just before the crash, police said.
The Santa Clara County medical examiner's office will determine the cause of death.
Traffic was blocked on Middlefield Road while the crash was investigated, and Santa Clara Valley Transit Authority bus line No. 35 was rerouted.
Anyone with information on the crash is asked to call the Police Department's 24-hour dispatch center at (650) 329-2413. Those wishing to remain anonymous can call or text (650) 383-8984, or email paloaltotipnow.org.