The Paris fire service has said the next hour is "crucial" to see if the blaze can be contained.
Firefighters have also warned the north tower could collapse.
Paris authorities have admitted that getting fire fighters to the top of the building is proving to be "almost impossible".
Reports say Notre Dame bosses are pessimistic about the famous 850-year-old building being saved.
Cardinal Vincent Nichols, Archbishop of Westminster, said: “The shock at the outbreak of this fire is spreading around the world.
“It is an iconic building visited by millions, but more importantly it is a symbol of faith which is at the heart of Europe.”
Enormous plumes of smoke can be seen billowing into the Paris skyline.
The building was evacuated just after 5.50pm (GMT) with witnesses describing ash falling as flames burst from the flaming cathedral.
French newspaper Le Monde reported that the fire broke out in the attic of the historic cathedral before spreading to the roof.
An investigation has reportedly been launched by the Paris Public Prosecutor’s Office.
This is being handled by the Regional Directorate of the Judicial Police.
It is unclear why the investigation has been launched, but initial reports in Paris are saying it was caused by an accident during renovation works.
Political figures across the globe have responded to the devastating scenes unfolding.
French President Emmanuel Macron has cancelled a planned address to the nation in light of the horrifying blaze.
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!"
Deputy Labour Party leader Tom Watson tweeted: "Absolute tragedy unfolding. I hope the Parisians can save their beautiful Cathedral. #NotreDame"
Paris mayor Anne Hidalgo described it as a "terrible fire" and urged people at the scene to stay safe.
French President Emmanuel Macron tweeted: "Our Lady of Paris in flames. Emotion of a whole nation. Thought for all Catholics and for all French. Like all our countrymen, I'm sad tonight to see this part of us burn."