The American official traveling with Secretary of State Hillary Clinton in Africa called on other senior members of the Syrian government and military to break with President Bashar Assad.
The Jordanian government and the Syrian rebels said Prime Minister Riad Hijab had fled to neighboring Jordan. The rebels said three other ministers also had defected.
The U.S. official spoke on condition of anonymity because the official was not authorized to speak publicly on the matter. The official said the U.S. is trying to confirm reports of the defections.
Clinton will stop in Turkey for talks on Syria on Saturday.
Meanwhile, in Washington, the White House said the defection indicates the momentum is with opposition forces and the Syrian people.
National Security Council spokesman Tommy Vietor said the defections are reaching the highest levels of the Syrian government and demonstrate that the Syrian people believe Assad's days are numbered.
Vietor said the quickest way to end the bloodshed in Syria is for Assad to recognize that the Syrian people will not allow him to continue in power. And Vietor renewed U.S. calls for Assad to leave power and allow for a political transition.