"After 13 years of civil war in Syria, more than half a century of brutal authoritarian rule by Bashar al-Assad and his father before him, rebel forces have forced Assad to resign his office, flee the country," Biden said at the White House on Sunday.
"At long last, the Assad regime has fallen," Biden said.
"This regime brutalised, tortured and killed literally hundreds of thousands of innocent Syrians."
He called the fall of the regime "a fundamental act of justice".
Syrian rebels have seized control of Damascus, ousting President Bashar al-Assad. (AP PHOTO)
Biden spoke hours after after rebel groups completed a takeover of the country following more than a dozen years of violent civil war and decades of leadership by Assad and his family.
The outgoing Biden administration and President-elect Donald Trump were working to make sense of new threats and opportunities across the Middle East.
Biden, who leaves office on January 20, said that the United States would not allow the Islamic State terrorist group, which still has a presence in Syria, to exploit the power vacuum to regain its influence in Syria.
There are around 900 US soldiers stationed in Syria tasked with combating the Islamic State.
Biden said that in the past few hours US forces carried out "precision airstrikes" on Islamic State targets in Syria.
"We're clear-eyed about the fact that ISIS will try and take advantage of any vacuum to re-establish its credibility, and create a safe haven," Biden said, using a different acronym for the group.
"We will not let that happen."
"We will remain vigilant," he assured. This vigilance, he said, also applies to the rebel groups that had toppled al-Assad.
"Make no mistake, some of the rebel groups that took down Assad have their own grim record of terrorism and human rights abuses."
The US government will also support Syria's neighbouring countries including Jordan, Lebanon, Iraq and Israel should a threat emanate from Syria, Biden said, calling it "a moment of risk and uncertainty" for the Middle East.
with AP
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