Firefighters from San Bruno and surrounding cities are battling the blaze that started on a hillside and is now consuming homes in a residential neighborhood.
Television live shots show at least a dozen homes destroyed, with flames reaching now as high as 50 to 60 feet into the air.
A South San Francisco fire official confirmed earlier that firefighters were responding to a fire, but had no other details.
Witnesses say a loud explosion was felt just before the flames erupted around 6 p.m. Thursday.
The fire is burning in a mostly residential area a few miles from San Francisco International Air, but the Federal Aviation Administration and a spokesman for the airport say they have no record of a plane crash.