The 850-year-old Gothic building, but its spire and roof have collapsed.
The cause is not yet clear, but officials say that it could be linked to renovation work.
Last year, the Catholic Church in France appealed for funds to save the building, which was crumbling.
Loud bangs could be heard as flames burst through the cathedral's roof, also engulfing its left tower.
A spokesman for the cathedral said the whole structure was "burning".
"There will be nothing left," he said. "It remains to be seen whether the vault, which protects the cathedral, will be affected or not."
Historian Camille Pascal told French broadcaster BFMTV the fire was destroying "invaluable heritage."
"For 800 years the Cathedral has watched over Paris", he said.
"Happy and unfortunate events for centuries have been marked by the bells of Notre Dame.
"We can be only horrified by what we see".