Dramatic images posted to social media showed the roof of the medieval cathedral engulfed in flames.
A Paris fire department spokesperson told Reuters that the area was being cleared and a large-scale operation was underway to address the blaze.
There was no immediate word on the cause of the blaze, but the structure has been undergoing a $6.8 million renovation project, including work on its spire.
The monument sees over 13 million visitors a year and is Paris's most visited attraction, beating the Eiffel Tower, according to the city's tourism report.
It was not immediately known what caused the fire and whether anybody was injured.
One man now in the city wrote on Twitter: "Unreal".
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Notre Dame was constructed in 1163 during the reign of King Louis VII and was completed in 1345.
"Last January, I looked out over the Parisian skyline, all the more beautified by the cathedral's spire", he added.
Flames that began in the early evening burst through the roof of the centuries-old cathedral and engulfed the spire, which collapsed, quickly followed by the entire roof. Trump said it was "horrible" to watch and said perhaps flying water tankers could be used. The cathedral, which is located on one of two islands in the middle of the Seine River, had been under renovation and scaffolding covered much of the roof.
French President Emmanuel Macron postponed a televised speech to the nation because of the stunning blaze.
Hidalgo urged residents of the French capital to stay away from the security perimeter around the Gothic-style church. "Our hearts are with the citizens of France and the tales of Notre Dame, true and fictional, in prayer that they will endure forever".
London Mayor Sadiq Khan has said his city "stands in sorrow with Paris today". Thought for all Catholics and for all French.
Anne Hidalgo, the mayor of Paris, tweeted, "A bad fire is underway at Notre Dame Cathedral in Paris".