Speaking at the UN General Assembly, Obama described Assad as a tyrant and as the chief culprit behind the four-year civil war in which at least 200,000 people have died and millions have been driven from their homes internally or abroad as refugees.
"The United States is prepared to work with any nation, including Russia and Iran, to resolve the conflict," Obama said at the annual gathering of world leaders. "But we must recognize that there cannot be, after so much bloodshed, so much carnage, a return to the pre-war status quo."
In voicing a willingness to deal with Iran and Russia, both staunch backers of Assad, Obama was openly acknowledging their influence in Syria and swallowing a somewhat bitter pill for the United States.
Tehran has armed the Syrian government and, through its backing of Lebanese Hezbollah fighters, has helped Assad fight rebels seeking to end his family's four-decade rule. Russia has recently engaged in a military build-up in Syria, where it has a naval base that serves as its foothold in the Middle East.Obama is scheduled to meet Russian President Vladimir Putin later on Monday on the sidelines of the gathering, for talks that could provide some hint on how it might be possible to end a conflict that has defied years of diplomatic efforts.