In what the local weather agency said was some of the worst flash floods the Aude river has seen in more than a century, the heavy rainfall brought raging torrents that engulfed homes and swept away cars.
Residents in the region have been told to remain indoors and more than 700 firemen and several helicopters have been sent to bolster the rescue effort.
Authorities said many people were stranded on rooftops and would have to be evacuated by air because it was too dangerous by boat.
Several deaths were in the town of Trebes, which sits between a canal and two rivers, including the Aude.
A nun was swept away by the rapid waters, according to local broadcaster BFMTV, while other reports said a policewoman was hit by a motorist while attending a weather related traffic accident.
“It’s like a war zone,” said Jean-Jacques Garros, a resident of Villegailhenc, one of the hardest hit areas.
The Interior Ministry initially put the number of deaths at 13 before revising the toll downwards to 12, though it could rise again.
Prime Minister Edouard Philippe flew to the disaster zone to meet with emergency service personnel.
As the death toll rose and the extent of the damage became clear, President Emmanuel Macron decided to hold off on an already-delayed reshuffle of his cabinet.
Television pictures showed churning, muddy rivers that had uprooted trees, knocked over concrete power pylons and tore up roads in the southern region of Aude, near the medieval hilltop city of Carcassonne.
Among the worst hit were the villages of Conques-sur-Orbiel, Villegailhenc and Villardonnel, where the water rose as high as the first-floor windows of some houses.
The Aude region is a popular tourist destination with old towns and villages in its hilly peaks and land stretching down to the Mediterranean.
The flash floods struck without warning. At least one victim was carried away by raging waters while sleeping, according to Alain Thirion, the prefect of Aude.
The Vigicrues agency, which tracks water levels in France, said the flooding was nearing a peak last seen in 1891.
Torrential downpours are not uncommon in France at this time of year, but meteorologists have said that exceptionally warm sea water along the Mediterranean coast may have intensified the rains.
The year so far is France’s warmest since 1900, according to the state meteorological service.