The Dorchester Group, which runs Plaza Athenée, did not give a reason for the decision to part ways, but confirmed that Ducasse will continue to collaborate at their other restaurants, le Meurice in Paris and The Dorchester in London.
The separation, effective from 30 June, is being presented as by mutual agreement.
Ducasse, who is 64-years-old and has picked up 21 Michelin stars in his career, was most recently in the headlines for his radical decision to quit using two staples of French cooking: meat and butter.
He remodelled the kitchen around fish, grains and vegetables, and it proved another huge hit with critics, pointing towards a new direction for French top-class cooking.
His award-winning pastry chef Jessica Prealpato took an even more radical step by applying the Ducasse ethos to desserts.
"La desseralité" meant using very little sugar and ingenious concepts such as freeze-drying fruits in vinegar to draw out their flavours.
A blow to high-end gastronomy
Franck Pinay-Rabaroust, editor-in-chief of the specialist publication Atabula, says "it's a slap in the face for the man, and an earthquake for high-end French gastronomy."
Pinay-Rabaroust goes on to suggest that Ducasse could soon be wielding his spatula in the kitchens of up-market rival The Ritz.
A spokesman said Ducasse's "naturalness" campaign had "left its mark on the history of gastronomy".
The move comes as haute cuisine, like the rest of the French restaurant business, prepares to emerge from an unprecedented hibernation caused by the Covid pandemic, with top restaurants in western Europe robbed of their ultra-rich, globe-trotting clientele.
During the pandemic, Ducasse sought to bring his cuisine to the people, offering takeaway dishes for just 22 euros.
