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.
A spokesman said the entire wooden frame of the cathedral would likely come down, and that the vault of the edifice could be threatened too.
Speaking to BFMTV, Deputy Mayor Emmanuel Gregoire said first responders now trying to salvage the art and other priceless pieces stored in the cathedral.
Notre Dame Cathedral has gone up in flames this evening in a roaring blaze that devastated the Parisian landmark, leaving the city, France, and the worldwide community distraught. To cover the rest, Picaud helped launch the Friends of Notre-Dame of Paris Foundation.
Macron tweeted "emotion of a whole nation" on seeing Notre-Dame ablaze. France's President Emmanuel Macron will be visiting the site later, according to a government spokesperson.
It was not immediately clear what had caused the fire.
Paris' Notre Dame Cathedral, one of the most famed examples of Gothic architecture, has been heavily damaged by flames.
Parts of the roof has collapsed and its spire has dramatically toppled over. He suggested that France should get some "flying water tankers" to put out the blaze.
Even President Donald Trump was following the fire.
Notre Dame has enjoyed a special place in literature and film as the subject of Victor Hugo's 1831 novel The Hunchback of Notre Dame, which was made into a popular animated movie by Disney in 1996. "Our thoughts and prayers are with the firefighters on the scene and all the people of Paris".
"A awful fire is underway at Notre Dame Cathedral", Mayor Anne Hidalgo tweeted, according to a translation from CNN.
"We express our solidarity to French Catholics and to the people of Paris and we offer our prayers for firefighters and those who are doing what is possible to face this dramatic situation", said Gisotti.
The Metropolitan Museum of Art in NY also expressed its condolences, tweeting, "The Met and the collective cultural community are watching in shock and horror at the fire engulfing Notre-Dame Cathedral". The cathedral is a worldwide Parisian icon and site of some of Catholicism's most important relics, including the crown of thorns said to have been worn by Jesus.