Images from the scene show trees on fire and buildings burned and hollowed out.
Firefighters had been working to fight back the blaze but on Wednesday night it blew through the line and swept into Greenville.
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“We lost Greenville tonight,” said Congressman Doug LaMalfa, who represents the region.
“There’s just no words.”
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Firefighters also had to deal with people reluctant to leave and their refusals meant that they spent time loading people into cars to ferry them out, said Jake Cagle, an incident management operations section chief.
“We have firefighters that are getting guns pulled out on them because people don’t want to evacuate,” he said.
The fire covers almost 504 sq miles and only 35% of it was contained on Thursday.
A petrol station, church, hotel, museum and bar were among fixtures gutted in the town dating back to California’s Gold Rush era, which had some wooden buildings more than 100 years old.
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Wildfire causes eerie Martian glow in US
To the northwest, crews were protecting homes in Chester.
Residents there were among thousands under evacuation orders or warnings across several counties, but no injuries or deaths have been reported.
Scientists say climate change has made the region much warmer and drier in the past 30 years and will continue to make weather more extreme and wildfires more frequent and destructive.
More than 20,000 firefighters and support personnel are battling 97 wildfires covering 2,919 sq miles (7,560 sq km) in 13 American states, the National Interagency Fire Center said.