Strong winds prevented firefighters from saving the south wing of the Luneville chateau, near Nancy, where some of the most important rooms were located.
Volunteers formed a human chain to rescue some of a precious collection of china, but the majority was destroyed.
"It's a terrible shock," said local mayor Michel Closse. "It's a catastrophe, the damage is considerable."
Looting risk
The cause of the fire, which began in the roof of the chapel, is under investigation, though officials have suggested it could have been an electrical fault.
The royal apartments of Louis XV's father-in-law, the dethroned King Stanislas of Poland, were among those rooms destroyed.
Efforts to save the china continued until the last possible moment, when the roof of the museum gallery began to collapse.
Pottery has been made at Luneville since the 18th Century. The chateau's collection went back to the early 1700s.
Many of the chateau's windows were blown out, and a security cordon was placed around it to prevent looting.
Seventh fire
It took 150 firefighters several hours to bring the blaze under control, amid winds gusting at up to 100km/h (60 mph).
They successfully struggled to prevent the flames spreading to a nearby theatre made entirely of wood.
The chateau was built by the architect Germain Boffrand for Duke Leopold of Lorraine.
Its hayday was under Stanislas, the dethroned King of Poland, who made it his home and welcomed writers and philosophers such as Voltaire.
This is at least the seventh fire at the chateau, the most recent of which, in 1961, ruined the roof and left two firefighters injured.