President Joe Biden addressed the nation Sunday after meeting with his national security team, calling the fall of Syrian President Bashar al-Assad's "abhorrent" regime a "historic opportunity for the long-suffering people of Syria."

"At long last, the Assad regime has fallen," Biden said. "This regime brutalized, tortured and killed literally hundreds of thousands of innocent Syrians."

At the same time, it's "also a moment of risk and uncertainty," Biden added, saying that the U.S. would "support Syria's neighbors, including Jordan, Lebanon, Iraq, and Israel, should any threat arise."

He also said the U.S. is "mindful" of the security of Americans in Syria, including American freelance journalist and Marine Corps veteran Austin Tice, who was kidnapped while reporting in Syria in 2012. Biden said it will "remain committed to returning [Tice] to his family."

"This is a moment of considerable risk and uncertainty," Biden said. "But I also believe this is the best opportunity in generations for Syrians to forge their own future free of opposition."

President-elect Donald Trump had earlier called the situation in Syria a "mess" and urged against the U.S. getting involved in the conflict.

"In any event, Syria is a mess, but is not our friend, & THE UNITED STATES SHOULD HAVE NOTHING TO DO WITH IT. THIS IS NOT OUR FIGHT. LET IT PLAY OUT. DO NOT GET INVOLVED!" Trump wrote in a post on X.

On Saturday, White House National Security Council spokesperson Sean Savett said the U.S. "has nothing to do with this offensive, which is led by Hay’at Tahir al-Sham (HTS), a designated terrorist organization," and said that the U.S. would work together with its allies and partners to urge deescalation and to protect U.S. personnel and military positions.

Speaking at a defense conference Saturday, before rebels advanced into Damascus, national security adviser Jake Sullivan said the speed and scale of the rebels' rapid advance came, in part, because Assad's chief backers -- Iran, Russia and Hezbollah -- had all been "weakened and distracted," in recent months.

That has left Assad "basically naked," Sullivan said. "His forces are hollowed out."

Secretary of State Antony Blinken said in a statement Sunday evening that the fall of Assad's regime means "the Syrian people finally have reason for hope."

"The United States strongly supports a peaceful transition of power to an accountable Syrian government through an inclusive Syrian-led process," Blinken said. "During this transitional period, the Syrian people have every right to demand the preservation of state institutions, the resumption of key services, and the protection of vulnerable communities."

Early Sunday, the rebel military operations command for the Islamist Hayat Tahrir al-Sham group, or HTS, claimed the president was no longer in the capital, writing: "We declare the city of Damascus free of the tyrant Bashar al-Assad."

The Russian Foreign Ministry said Sunday morning that Assad "decided to leave the presidential post and left the country, giving instructions to transfer power peacefully." Russia and Iran were the two most important foreign backers of Assad's government.

Trump said Russia, which has long supported Assad's regime, is "tied up in Ukraine" and apparently unable to intervene in Syria, and said Assad being forced out "may actually be the best thing that can happen" to the Russian government.

"There should be an immediate ceasefire and negotiations should begin. Too many lives are being so needlessly wasted, too many families destroyed, and if it keeps going, it can turn into something much bigger, and far worse," Trump said.

In an interview with ABC News, retired Marine Corps Gen. Frank McKenzie, who led U.S. Central Command during Trump's first term, agreed with the president-elect's assessment that the situation could spell chaos.

"I’m not sure it's ultimately going to be good news for the people of Syria," McKenzie told "This Week" co-anchor Martha Raddatz. "You know, we could have an Islamic State arise there which will have profound negative implications across the region. That is possible. There are other possibilities as well. And I think in the next 48, 72, 96 hours, we -- this will begin to become clearer to us."

"It's a significant moment in Syrian history," McKenzie added. "I wish I could be more hopeful that it will mean good news for the Syrian people. I think that's very unclear right now."

Asked about the safety of the 900 U.S. military members stationed in eastern Syria to contain ISIS, McKenzie said Assad's fall could put them in a better place.

"Actually, there's probably less danger right now than there was before, because what you see are the Iranians, Lebanese Hezbollah and, in fact, the Russians are all on their back heels now as a result of what has just happened in Syria," he said.

The regime's collapse marks an end to a 24-year reign, Assad having succeeded his father Hafez al-Assad in 2000. The Assad family had ruled Syria since 1971.

Assad oversaw Syria's slide into brutal civil war in 2011. His security forces sought to crush a mass protest movement demanding democratic reforms as the Arab Spring buffeted the region. The standoff devolved into a bloody civil war that split the nation on political, ethnic and religious lines.

The chaos allowed ISIS to rise in the Iraq-Syria border region and seize swaths of territory in the Levant region. The conflict also became a proxy battleground drawing in major world powers including the U.S., Russia, Iran, Israel and the Gulf states.

The United Nations estimated some 307,000 civilian dead in Syria by the end of 2022, with 12 million people -- more than half of the country's 2011 population of around 22 million -- forced from their homes, approximately 5.4 million of whom were still living as of late 2022.