A "significant fire" broke out at the iconic Notre Dame Cathedral in central Paris at 7 pm local time, according to the national police.
Smoke could be seen billowing out from the top of the medieval cathedral, as flames leapt out beside its two bell towers.
Both the spire and roof of the cathedral have now collapsed.
Footage from the scene showed flames inside one of the building's two towers.
NBC journalist Nancy Ing reported that "gargoyles are falling off the roof".
No injuries have been reported at this stage, according to French Junior Interior Minister Laurent Nunez.
The Paris Prosecutor has opened an official investigation to determine the cause.
Nicolas Marang, 47, a consultant and a Paris resident for 27 years who witnessed and took a video of Notre Dame's spire falling, told Euronews the blaze was "an absolute nightmare".
"I keep thinking about, all the culture. It is so delicate and now it's all gone. It's all burned," he said.
"People started taking pictures. Some people were crying. It was like being knocked out," he added.
French President Emmanuel Macron and Prime Minister Edouard Philippe have arrived at the scene along with the Prosecutor.
A major operation is underway, the fire department said, while a city hall spokesman said on Twitter that the area was being cleared.
"A terrible fire is underway at Notre-Dame Cathedral in Paris," mayor Anne Hidalgo wrote on Twitter. "Firefighters are trying to control the flames ... I invite everyone to respect the security perimeter."
Police advised people to avoid the area in a tweet and requested that they facilitate the passage of emergency and vehicle.
A group of 16 copper statues escaped the blaze as they were removed from the cathedral's roof on April 11 for restoration work, as part of a €6 million rennovation project.
French President Emmanuel Macron cancelled a planned 8 pm CEST address to the nation on the "gilets jaunes" (yellow vests) movement due to the "terrible fire", said an official at the president's Elysee office.
