André Finot, a spokesman for the cathedral, told the New York Times in a telephone interview that the spire of the cathedral had caught fire. Notre Dame was first constructed in 1160 and later restored between 1845 and 1870.
Firefighters cleared the area around Notre-Dame, which sits on an island in the River Seine and marks the very centre of Paris.
Cardinal Timothy Dolan, the archbishop of NY, said he was praying "to ask the intercession of Notre Dame, our Lady, for the Cathedral at the heart of Paris, and of civilization, now in flames!"
Others described the tragedy of never being able to see the Notre Dame as it was before the blaze.
Given the scale of the damage to the handsome landmark, it is unlikely visitors will be able to visit.
Update 2:10 p.m.: President Trump has lamented the fire.
Express.co.uk has contacted Notre Dame for further comment on visitor information.
He recalled that Notre Dame bells sounded the death knell following the 2015 Paris attacks.
London Mayor Sadiq Khan has said his city "stands in sorrow with Paris today".
The cause of the blaze was not immediately confirmed, but the cathedral had been undergoing intense restoration work to help the 850-year-old Gothic masterpiece better deal with the tests of time.
The building is in the midst of renovations and is now wrapped in scaffolding.
Images circulating on social media showed parts of its roof on fire. Paris firefighters are trying to control the flames.
A spokesman from Elysee Palace said French President Emmanuel Macron will visit the scene. Trump said it was "horrible" to watch and said perhaps flying water tankers could be used.
"September 11 attacks, also called 9/11 attacks, series of airline hijackings and suicide attacks committed in 2001 by 19 militants associated with the Islamic extremist group al-Qaeda against targets in the United States, the deadliest terrorist attacks on American soil in US history", the panel read.
"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".