Just after 1 p.m. videos began to be posted to social media about smoke billowing from the roof.
The cathedral is one the finest example of French Gothic architecture in Europe, and one of the most visited buildings in the world.
The cause of the blaze isn't yet known, but scaffolding could be seen on the roof of the burning structure.
A major operation was under way, the fire department said, while a city hall spokesman said on Twitter that the area was being cleared. "London stands in sorrow with Paris today, and in friendship always", London Mayor Sadiq Khan wrote on Twitter.
A massive fire overtook the 850-year-old Notre Dame Cathedral in France on April 15, bringing parts of the legendary building down in a rain of ash and flames.
"Last January, I looked out over the Parisian skyline, all the more beautified by the cathedral's spire", he added. He suggested that France should get some "flying water tankers" to put out the blaze.
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Authorities are investigating if renovation work on the cathedral's spire was a factor in starting or spreading the fire.
Macron was also headed to the scene after postponing a much-anticipated speech on planned policy measures following a long series of violent protests by the Yellow Vest movement that rocked the capital.
Paris deputy mayor Emmanuel Gregoire said emergency services are trying to salvage the famed art pieces stored in the cathedral.
Flames and black smoke were seen shooting from the base of the medieval church's spire on Monday.
"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.
"Heart-breaking scenes of Notre Dame cathedral in flames".
The peak of the church is undergoing a $6.8 million renovation project.