Gasps and cries of "Oh my god" erupted at 7:50 pm (1750 GMT) when the top portion of the church's spire came crashing down into an inferno that has spread to the entire roof.
More gasps came a few seconds later when the rest of the spire collapsed, caught on the cameras of thousands of mobile phones.
"Paris is disfigured. The city will never be like it was before," said Philippe, a communications worker in his mid-30s, who had biked over after being alerted of the fire by a friend.
"It's a tragedy," he added. "If you pray, now is the time to pray."
Police were attempting to clear pedestrians away from the two islands in the river Seine, including the Ile de la Cite which houses the soaring Gothic church, one of Europe's best known landmarks.
But throngs of onlookers kept trying to approach, snarling traffic as they massed on the stone bridges leading to the islands.
Another woman passed by, tears running from behind her glasses, too overwhelmed to speak to reporters.
"It's finished, we'll never be able to see it again," said Jerome Fautrey, a 37-year-old who had come to watch.
"Now we need to know how this happened -- with everything that's going on in the world, why Notre-Dame? Maybe it's a message from on high," he said.
One police officer, arriving on one of the bridges, turned up to gape, saying "Oh my god."
"It's incredible, our history is going up in smoke," said Benoit, 42, who arrived on the scene by bike.