"The fight against Daesh is crucial, but it will only be totally effective if all the Syrian and regional forces are united," he told the French regional newspaper Le Progres, using an Arabic acronym for the Islamic State group.
"A united Syria implies a political transition. That does not mean that Bashar al-Assad must leave even before the transition, but there must be assurances for the future".
The comments mark a change in France's position on the Syrian president, as it has previously demanded the removal of Assad, describing him as a "butcher" of his own people.
France, like the United States and members of the international coalition waging an air campaign against IS in Syria and Iraq, is seeking political or military options involving all the local and regional parties to find a solution to the four-year-old war in Syria.
Fabius on Monday said that it was "obvious" Assad could not work alongside moderate rebels in Syria.
"If we achieve a political transition and it's no longer Bashar in charge of the Syrian army, there could be joint actions against terrorism. But under Bashar it's not possible," Fabius told France Inter radio on Monday, speaking at the UN climate conference just outside Paris.
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