PARIS—French President Emmanuel Macron said removing Syrian leader Bashar al-Assad from power shouldn’t be a precondition for a peace deal in the war-torn nation, a shift in French policy after years of Paris calling for Mr. Assad to step aside.

“The real update I have done on this subject,” Mr. Macron said in an interview with European newspapers, when asked about Syria, “it’s that I have not announced that the removal of Bashar al-Assad is a precondition for everything. Because no one has showed me a legitimate successor.”

Mr. Macron’s comments mark his first major foreign policy departure from his predecessor, François Hollande, who has insisted since the early days of Syria’s bloody civil war that Mr. Assad should step down. Mr. Macron took office last month after winning the election in a landslide.

Mr. Macron added that he had found some common ground with Russian President Vladimir Putin, a key supporter of Mr. Assad, on the question of Syria. The two leaders met in Versailles outside Paris last month.

“We’ve been blocked for a long time on the figure of Bashar al-Assad,” Mr. Macron said, “But Bashar, he is not our enemy. He is the enemy of the Syrian people.”

Mr. Macron, however, drew a “red line” against Mr. Assad using chemical weapons, after the international community accused the Syrian regime of unleashing sarin gas in April on rebel-held areas, killing scores of people. U.S. President Donald Trump ordered cruise missile strikes against a Syrian military air base in retaliation. Mr. Macron said that France would conduct airstrikes if Mr. Assad used chemical weapons again, with or without French allies.

“If it’s found that chemical weapons are used on the ground and that we know the origin, France will then proceed to strikes to destroy stocks of chemical weapons,” he said.

Mr. Macron’s remarks could spark debate within Europe about the bloc’s diplomatic stance on the Syrian conflict. European diplomats have long called on Mr. Assad to step aside after six years of brutal civil war, in which tens of thousands of people have died at the hands of regime forces.

“The EU recalls that there can be no lasting peace in Syria under the current regime,” the bloc’s foreign ministers said in a statement in April.

France is a major contributor to the U.S.-led military coalition fighting Islamic State in Iraq and Syria. French jets fly bombing missions out of regional air bases, while French artillery batteries and special forces are fighting the extremist group on the ground.

Tensions have flared recently between Russia and the coalition. A U.S. jet fighter shot down a Syrian government plane that dropped bombs near U.S.-backed forces that are bearing down on Raqqa, Islamic State’s de facto capital in northern Syria. Russia responded by threatening to shoot down coalition planes operating west of the Euphrates River.