The Vatican said: "The Holy See has seen with shock and sadness the news of the terrible fire that has devastated the Cathedral of Notre Dame, symbol of Christianity in France and in the world."
France's civil security agency says "all means" except for water-dropping aircraft were deployed to tackle the blaze.
The defense agency said those were unsuitable for fires like the one at Notre Dame because dumping water on the building could cause the whole structure to collapse.
Paris police say fighters are inside the cathedral working to put the flames out while others work from the exterior. Red smoke is pouring out of the cathedral.
French President Emmanuel Macron is treating the fire gutting Notre Dame Cathedral as a national emergency.
The Vatican is praying for firefighters "and those who are doing everything possible to confront this dramatic situation" on Monday.
It also expressed "our closeness to French Catholics and the population of Paris, and we assure our prayers for firefighters
The peak of the church is undergoing a 6 million-euro ($6.8m) renovation project.
Flames and black smoke were seen shooting on Monday from the base of the medieval church's spire.
A church spokesperson says the entire wooden interior of the 12th century landmark is burning and likely to be destroyed.
Notre Dame spokesperson Andre Finot told French media: "Everything is burning, nothing will remain from the frame."
A massive fire engulfed the roof of the cathedral in the heart of the French capital on Monday afternoon as Parisians watched in horror.
"This is really sad - the saddest thing I've ever stood and watched in my life," said British tourist Sam Ogden, a 50-year-old onlooker, who had come to visit the cathedral with her family.
Gasps and cries of "Oh my god" erupted around an hour after the fire first broke out when the top portion of the church's spire came crashing down.
"It looked tiny to begin with, then within an hour it all came down," Ogden added.
France 2 television reported that police were treating the incident as an accident.
According to AFP news agency, the fire was noticed at about 6:50pm local time (14:50 GMT).
The French capital's police department said no deaths have been reported from Monday's fire. The police department didn't say anything about injuries.
French media quoted the Paris fire brigade saying the fire is "potentially linked" to the renovation work.
Paris Mayor Anne Hidalgo says firefighters are trying to contain the "terrible fire".
Hidalgo urged residents of the French capital to stay away from the security perimeter around the Gothic-style church. The mayor says city officials are in touch with Roman Catholic diocese in Paris.
Macron's pre-recorded speech was set to be aired on later Monday on French TV.
Macron was expected to lay out his plan to address the citizen complaints that gave rise to the yellow vest protests that have rocked France since November.
He is now at scene of the fire, and will be heading into meetings with Paris police.
Notre Dame is distinguished for its size, antiquity and architectural interest.
The cathedral, which dates back to the 12th century and is famous for featuring in Victor Hugo's classic novel the Hunchback of Notre Dame, attracts millions of tourists every year.
Located on the Ile de la Cite in the center of Paris, the Gothic cathedral is among the most famous from the Middle Ages and was built on the ruins of two earlier churches.