Dozens of fire vehicles were at the scene while high-pressure hoses could be seen spraying water onto the collapsed roof and nave area, suspended from cranes.
"We are not sure we can stop the spread to the northern tower," junior Interior Minister Laurent Nunez warned reporters, referring to the two stone towers at the front of the Gothic masterpiece.
"If that collapses, you can imagine the scale of the damage," he added.
US President Donald Trump had suggested on Twitter that "flying water tankers" could be used to put out the blaze.
"Dumping water from a plane on this type of building would risk bringing down the whole edifice," France's Civil Security agency wrote on Twitter.
Paris deputy mayor Emmanuel Gregoire told the BFM news channel that firefighters had entered the cathedral and had brought out some of its priceless artworks.
But they had been forced to withdraw as the flames spread rapidly through the wooden beams holding up the roof.
"At the moment, the priority is to control the blaze on the inside and to protect the facade," he said, three hours after the fire broke out at around 6 pm (1600 GMT).
"Obviously we fear the worst in terms of damage given the scale of the fire."
"It's a difficult fire," a fire official told AFP at the scene.
The interior ministry said 400 firefighters were in action in a statement on Twitter.
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