Witnesses posted pictures to twitter Monday showing smoke billowing out of the building in France's capital.
The cathedral is 850 years old, and last year the Catholic Church launched an urgent appeal for funds to fix the building, which was showing serious signs of decay.
Paris police said there were no deaths so far and the origin of the fire was unknown. 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.
President Emmanuel Macron postponed his 8pm speech to head to the site of the fire.
We are deeply saddened by the ongoing fire at the Notre Dame cathedral. I've never seen a fire in real life but the flames keep getting bigger and bigger. We are mobilized locally in close connection with church authorities. "I invite each and every one to respect the perimeter of security".
French President Emmanuel Macron, who has arrived at the scene, said his thoughts were with "all Catholics and all French people". "Like all our compatriots, I'm sad tonight to see this part of ourselves burn".
"Notre Dame is an iconic symbol of faith to people all over the world - and it is heartbreaking to see a house of God in flames", Pence tweeted Monday.
A third person commented on the footage of the cathedral burning: "Can't bear watching it. Devastating". Construction began in 1160 CE, and took around 100 years to complete, though numerous renovations would be undertaken in the centuries since.
The French Gothic building is remarkable for its stained-glass rose window, flying buttresses and large spire. "Must act quickly", Trump offered his advice on Twitter.
"The weight of the water and the intensity of the drop at low altitude could indeed weaken the structure of Notre-Dame and cause collateral damage to the surrounding buildings", the agency said in a tweet.
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