Hundreds of firefighters mobilized to battle the blaze in the Herault and Aude departments, fueled by drought and strong winds.
It came a year after major blazes in the Corbieres region and days after a deadly heatwave across much of Europe, with another one forecast.
By late evening the fire had covered 800 hectares, according to the prefecture.
“The fire is contained at times,” a source in the prefecture told AFP around 11:00pm (2100 GMT), but “it is not under control.”
Conditions on the ground were difficult for firefighters, with no access routes in the hilly terrain. Water-dumping aircraft were being used.
Temperatures of around 30C combined with strong wind gusts drove the spread of the fire through low, very dry vegetation.
About 200 people were evacuated or confined in the communes of Pouzols-Minervois and Mailhac, officials said.
“The smoke was so thick, so suffocating that firefighters told us to leave,” said one evacuated woman, Danielle, 99, from Pouzols.
Two smaller blazes broke out in Rognac and Lancon-Provence near Marseille, according to local firefighters.