Biden spoke at the White House hours after after rebel groups completed a takeover of the country after more than a dozen years of violent civil war and decades of leadership by Assad and his family. Biden said the United States was unsure of Assad's whereabouts, but was monitoring reports he was seeking refuge in Moscow.
The outgoing Biden administration and President-elect Donald Trump were working to make sense of new threats and opportunities across the Middle East.
Biden credited action by the U.S. and its allies for weakening Syria's backers - Russia, Iran and Hezbollah. He said "for the first time" that they could no longer defend Assad's grip on power.
"Our approach has shifted the balance of power in the Middle East," Biden said, after a meeting with his national security team at the White House.
Trump said Sunday that Assad had fled his country, which his family had ruled for decades, because close ally Vladimir Putin, the Russian president, "was not interested in protecting him any longer."
Those comments on Trump's social media platform came a day after he used another post to decry the possibility of the U.S. intervening militarily in Syria to aid the rebels, declaring, "THIS IS NOT OUR FIGHT." The Biden administration had no intention of intervening, according to President Joe Biden's national security adviser.
The U.S has about 900 troops in Syria, including forces working with Kurdish allies in the opposition-held northeast to prevent any resurgence of the Islamic State group. Biden said he intended those for troops to remain, adding that U.S. forces on Sunday conducted "dozens" of what he called "precision air strikes" on Islamic State camps and operations in Syria.
The Syrian opposition that brought down Assad is led by Hayat Tahrir al-Sham. The Biden administration has designated the group as a terrorist organization and says it has links to al-Qaida, although Hayat Tahrir al-Sham says it has since broken ties with al-Qaida.
"We will remain vigilant," Biden said. "Make no mistake, some of the rebel groups that took down Assad have their own grim record of terrorism and human rights abuses." He added that the groups are "saying the right things now."
"But as they take on greater responsibility, we will assess not just their words, but their actions," Biden said.
Assad's fall adds to an already tense situation throughout much of region on many fronts, including Israel's war with Hamas in Gaza and its fragile cease-fire with Hezbollah in Lebanon.
Trump, who takes office Jan. 20, 2025, made a connection between the upheaval in Syria and Russia's war in Ukraine, noting that Assad's allies in Moscow, as well as in Iran, the main sponsor of Hamas and Hezbollah, "are in a weakened state right now."
Vice President-elect JD Vance, a veteran of the U.S.-led war in Iraq, wrote on own social media Sunday to express skepticism about the insurgents.
"Many of 'the rebels' are a literal offshoot of ISIS. One can hope they've moderated. Time will tell," he said, using another acronym for the group.
Trump has suggested that Assad's ouster can advance the prospects for an end to fighting in Ukraine, which was invaded by Russia in February 2022.
Trump wrote that Putin's government "lost all interest in Syria because of Ukraine" and the Republican called for an immediate cease-fire, a day after meeting in Paris with the French and Ukrainian leaders.
Daniel B. Shapiro, a deputy assistant secretary of defense for the Middle East, said the American military presence will continue in eastern Syria but was "solely to ensure the enduring defeat of ISIS and has nothing to do with other aspects of this conflict."
"We call on all parties in Syria to protect civilians, particularly those from Syria's minority communities to respect international military norms and to work to achieve a resolution to include the political settlement," Shapiro said.
"Multiple actors in this conflict have a terrible track record to include Assad's horrific crimes, Russia's indiscriminate aerial bomb bombardment, Iranian-back militia involvement and the atrocities of ISIS," he added.
Shapiro, however, was careful not to directly say Assad had been deposed by the insurgents.
"If confirmed, no one should shed any tears over the Assad regime," he said.
As they pushed toward the Syrian capital of Damascus, the opposition freed political detainees from government prisons. The family of missing U.S. journalist Austin Tice renewed calls to find him.
"To everyone in Syria that hears this, please remind people that we're waiting for Austin," Tice's mother, Debra, said in comments that hostage advocacy groups spread on social media. "We know that when he comes out, he's going to be fairly dazed & he's going to need lots of care & direction. Direct him to his family please!"
Tice disappeared in 2012 outside Damascus, amid intensification of what became a civil war stretching more than a decade.
We've remained committed to returning him to his family," Biden said at the White House. "We believe he's alive, we think we can get him back but we have no direct evidence to that yet. And Assad should be held accountable."
The president added: "We have to identify where he is."
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Associated Press writer Jon Gambrell in Manama, Bahrain, and AP White House Correspondent Zeke Miller contributed to this report.