Pilot Andre Borschberg took to the air just after 5:00 am (12:00 GMT). The plane had been in California for a week since crossing the Pacific to land in Mountain View.
Borschberg, who has been alternating the long solo flights with his teammate, Swiss adventurer Bertrand Piccard, will pilot Solar Impulse across the United States and to New York. Piccard piloted the craft from Hawaii to California.
The mission aims to promote the use of renewable energy, with an aircraft powered by 17,000 solar cells.
The plane's wingspan is wider than that of a jumbo jet but its weight is roughly the same as a family car.