A United Nations human rights team says government forces in Syria "may amount to crimes against humanity." U.N. investigators say Syria should be referred to the International Criminal Court.
"His calls for dialogue and reform have rung hollow while he is imprisoning, torturing, and slaughtering his own people," Obama said in a statement. "We have consistently said that President Assad must lead a democratic transition or get out of the way. He has not led. For the sake of the Syrian people, the time has come for President Assad to step aside."
The demand for Assad to step down was accompanied by an executive order freezing all Syrian government assets in the U.S. and targeting the country's lucrative energy sector.
The move was coordinated with the United Nations and with U.S. allies in Europe and the Middle East and followed an intense diplomatic campaign to increase pressure on Assad. The European Union issued an identical call shortly after Obama's statement, followed quickly by similar words from the leaders of France, Britain and Germany.
Assad says military operations in his country have ended. Activists say security forces killed 18 people nationwide on Thursday.
The Associated Press contributed to this report.