Flames that began in the early evening burst rapidly through the roof of the centuries-old cathedral and engulfed the spire, which toppled, quickly followed by the entire roof.
As it burned into the evening, firefighters battled to prevent one of the main bell towers from collapsing. One firefighter was seriously injured - the only reported casualty.
"We now believe that the two towers of Notre-Dame have been saved," Paris fire chief Jean-Claude Gallet told reporters at the scene. "We now consider that the main structure of Notre-Dame has been saved and preserved."
There was still a risk that some of the interior structures could collapse, and firefighters would work overnight to cool them down, he said.
A huge plume of smoke wafted across the city and ash fell over a large area. People watching gasped as the spire folded over onto itself and fell into the inferno.
Firefighters battled smoke and falling drops of molten lead to salvage priceless artworks and relics.
A centuries-old crown of thorns made from reeds and gold and the tunic worn by Saint Louis, a 13th century king of France, were saved, Notre-Dame's top administrative cleric, Monsignor Patrick Chauvet said. But firefighters had struggled to take down some of the large paintings in time, he said.