At least 21 people were hospitalized, and one person has been reported dead.
It was estimated about 53 homes were destroyed and approximately 120 had been damaged.
By 11 p.m. Thursday, the fire was reportedly 50 percent contained and the gas main has been turned off.
The fire in San Bruno was burning in a hillside area a few miles from San Francisco International Airport, prompting speculation that the blaze was sparked by a plane crash. But a spokesman for the Federal Aviation Administration says the agency has no record of any plane crash. An airport spokesman also said there was no report of a plane down.
The utility company that serves the San Francisco Bay area said one of its gas lines ruptured in the area where a massive blast and fire destroyed homes and sent residents fleeing.
Pacific Gas and Electric Co. officials said in an e-mailed statement that the ruptured gas line was theirs, although they cautioned that the cause of the blast has yet to be determined.
The company said it would "take accountability" if it was found to be responsible for the explosion.
Witnesses said the blaze was preceded by a loud explosion and huge fireball. They described seeing residents fleeing for safety and rushing to get belongings out of their burning homes.
Television live shots showed at least a dozen homes destroyed, with flames reaching as high as 60 feet in the air as the fire fueled itself on the burning homes.
The Associated Press contributed to this report.