The cause is not yet clear, but officials say that it could be linked to renovation work.
A major operation to tackle the blaze is underway at the 850-year-old Gothic building, but the cathedral’s spire and roof have collapsed.
Last year, the Catholic Church in France appealed for funds to save the building, which was crumbling.
Hundreds of people have gathered in the streets around the cathedral, observing the flames in silence.
French President Emmanuel Macron, who has arrived at the scene, said his thoughts were with “all Catholics and all French people.”
“Like all of my countrymen, I am sad tonight to see this part of us burn.”
Mr Macron has cancelled his planned speech to the nation following the fire, an Élysée Palace official said.
A spokesman for the cathedral said the whole structure was “burning”.
“There will be nothing left,” he said. “It remains to be seen whether the vault, which protects the cathedral, will be affected or not.”
The blaze broke out on Monday afternoon and an area surrounding the building has been cleared.
Historian Camille Pascal told French broadcaster BFMTV the fire was destroying “invaluable heritage.”
“For 800 years the Cathedral has watched over Paris”, he said.
“Happy and unfortunate events for centuries have been marked by the bells of Notre Dame.
“We can be only horrified by what we see”.
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