A helicopter drops water on a backfire set by firefighters battling the Butte fire near San Andreas, California September 12, 2015. [Photo/Agencies]

Middletown and the town of Cobb, just to the north, were reported to be hardest hit by the flames, with large swaths of Middletown left in ruins, according to officials, eyewitnesses and local media reports.

Video footage from Middletown showed a smoking, devastated landscape of blackened, burned-out vehicles and the charred foundations of buildings that had been reduced to ash.

"While crews have not had a chance to do a full damage assessment ... we know 100s of structures have been destroyed," Daniel Berlant, a spokesman for the California Department of Forestry and Fire Protection, said in a Twitter post.

"This has been a very destructive fire. It has destroyed countless homes and other buildings," he said in a video news briefing released a short time later. "Evacuations are widespread in the area."

He said a combination of prolonged drought and a heat wave baking the region in triple-digit temperatures last week had left vegetation tinder dry and highly combustible, setting the stage for a conflagration that thwarted the best efforts of firefighters to contain it.

"Every time they made progress, the fire would burn right past them," he said, adding that stiff winds were carrying hot embers beyond the leading edge of the flames, sparking additional blazes that quickly enlarged the fire zone.

Four firefighters were hospitalized with second-degree burns after they were dropped off by helicopter to battle the fire, authorities said.