Dramatic pictures and videos shared on social media show smoke and flames rising from the landmark in France’s capital as huge crowds gather.
The blaze has spread to the giant spire of the medieval cathedral.
Firefighters confirmed a major operation was under way.
A city hall spokesman added that the area was being cleared.
Mayor Anne Hidalgo said on Twitter: “A terrible fire is underway at Notre-Dame Cathedral in Paris.”
French President Emmanuel Macron cancelled a planned address to the nation due to the “terrible fire”.
The blaze prompted a devastated reaction on social media.
And US President Donald Trump tweeted: “So horrible to watch the massive fire at Notre Dame Cathedral in Paris. Perhaps flying water tankers could be used to put it out. Must act quickly!”
The cause of the blaze at the 850-year-old Gothic building is not yet known.
France 2 television reported that police were treating the incident as an accident.
Officials said it could be linked to renovation works being carried out on the cathedral.
Parts of the building were covered by scaffolding while bronze statues were removed last week.
The cathedral dates back to the 12th century and is famous for its part in Victor Hugo’s novel the Hunchback of Notre-Dame.
It attracts millions of tourists every year.
More to follow.