Firefighters tried to contain the blaze with water hoses and cleared the area around Notre-Dame, which sits on an island in the River Seine and marks the very center of Paris.
Witnesses posted pictures to twitter Monday showing smoke billowing out of the building in France's capital.
A presidential official said Macron was to go to the scene of the blaze.
Paris Mayor Anne Hidalgo is in despair at the "terrible fire".
Evening sky in Paris lights up bright orange as massive fire causes the spire of Notre Dame Cathedral to collapse.
"There is no part of the building untouched by the irreparable loss of sculptural and decorative elements, let alone the alarming deterioration of structural elements", said the foundation.
While the cause of the fire remains unknown, renovations costing $6.8 million were being conducted at the historic cathedral, according to NBC News. As you'll see below, much of the roof, which was built with oak timbers that are 800 years old, has collapsed.
President Emmanuel Macron postponed his 8pm speech to head to the site of the fire.
Ashley Huntington, 21, an American university student studying in Paris, said: "Our class ran what was supposed to be 30 minutes walking but we probably got here in 20 running".
In a tweet he expressed the "emotion of a whole nation" on seeing Notre Dame ablaze. It is one of Europe's most-popular tourist attractions drawing about 12 million people a year to its doors.
The cathedral is "more than a historical monument", according to the translated cathedral website.
"Notre-Dame de Paris is in flames", he tweeted.
"A bad fire is underway at Notre Dame Cathedral", Mayor Anne Hidalgo tweeted, according to a translation from CNN.
This is a developing story.
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