Black smoke could be seen from a distance billowing out from the top of the medieval cathedral, while flames leaped out from two of its bell towers.
Paris Mayor Anne Hidalgo called it a "terrible fire."
The fire department was fighting the flames, while the area near the cathedral was being cleared.
It was not immediately clear what caused the fire. Notre Dame was undergoing a $6.8 million renovation project, with some sections under scaffolding, while bronze statues were removed last week for works.
Sources told Fox News that it appears the fire was related to recent construction done at the cathedral.
President Emmanuel Macron canceled a planned speech to the nation in light of the "terrible fire" underway at the cathedral, an official at the president's Elysee office said.
Additional information was not immediately available.
President Donald Trump tweeted about the fire, saying it was “horrible to watch the massive fire at Notre Dame Cathedral in Paris.
The cathedral, which dates back to the 12th century, was made famous for featuring in Victor Hugo’s novel “The Hunchback of Notre-Dame.” It attracts millions of tourists each year.