Mr Fabius - who was prime minister in the 1980s - was seen as the architect of France's tough foreign policy under President Francois Hollande.
He has been nominated by President Hollande to head France's constitutional court, which ensures bills comply with the constitution.
It is unclear who will replace Mr Fabius as foreign minister.
There had been reports of Mr Fabius's imminent departure as part of a wider cabinet reshuffle. He does not say why he was standing down.
Under Mr Fabius as foreign minister, over the past three years French forces have battled militants in Mali and taken part in air strikes against the Islamic State group in Syria and Iraq.
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