Obama will issue his call in a written statement on Thursday morning, and Secretary of State Hillary Rodham Clinton will echo the language soon after in an on-camera appearance. The administration will also slap new sanctions on Syria to bolster Obama's move.
Until now, the administration had said Assad had lost all credibility to rule with his ruthless crackdown on pro-reform demonstrators. The administration notified its Arab and European allies on Wednesday that Obama was going further and that an announcement was imminent.
Officials spoke on condition of anonymity because they were not authorized to discuss the matter.
Although the officials acknowledged the move is not likely to have any immediate impact on the Syrian regime's behavior, they said it would send a powerful signal that Assad is no longer welcome in the international community. And they noted that the additional sanctions would further boost pressure on Assad and his inner circle.
As Syrian protesters have called for an end to his regime, Assad has unleashed tanks and ground troops in an attempt to retake control in rebellious areas. The military assault has escalated dramatically since the start of the holy month of Ramadan in August, with Assad's forces killing hundreds and detaining thousands.
The administration had planned to make the announcement last week but postponed it largely at the request of Syria's neighbor Turkey, which asked for more time to try to convince Assad to reform, and because Clinton and other officials argued it was important to build a global consensus that Assad must go. Clinton on Tuesday publicly questioned the effectiveness of the United States acting alone.
"It is not going to be any news if the United States says Assad needs to go," she said. "OK, fine, what's next? If other people say it, if Turkey says it, if (Saudi) King Abdullah says it, there is no way the Assad regime can ignore it."
Since then, however, the coordination strategy appears to have borne fruit.
Ahead of the U.S. announcement, a high-level U.N. human rights team in Geneva said Thursday that Syria's crackdown "may amount to crimes against humanity" and should be referred to the International Criminal Court. U.N. High Commissioner for Human Rights Navi Pillay is expected on Thursday afternoon to urge the U.N. Security Council to make that referral
The investigators say they found "a pattern of human rights violations that constitutes widespread or systematic attacks against the civilian population." In their report, they said they had compiled a confidential list of 50 alleged perpetrators at "various levels" of Assad's government. Syria insists it is rooting out terrorists but rights groups accuse Syrian troops of killing more than 1,800 civilians since mid-March.
Jordan's foreign minister said Thursday that his country is "angered" and "extremely worried" by the killings of civilians in Syria and Switzerland recalled its ambassador. A day earlier, Tunisia recalled its ambassador from Syria, following the lead of several other Arab nations, including Saudi Arabia, that the U.S. has been lobbying to show displeasure with Assad.
Meanwhile, Turkish Prime Minister Recep Tayyip Erdogan on Wednesday has compared Assad to Libya's Moammar Gadhafi for refusing to heed calls to change. Turkey has joined calls for Gadhafi to leave power and Erdogan said Wednesday he had personally spoken to Assad and sent his foreign minister to Damascus, but "despite all of this, they are continuing to strike civilians."
In New York on Wednesday, U.N. Secretary-General Ban Ki-moon spoke to Assad demanding the immediate end of all military operations and mass arrests. In response, Assad said military and police operations had stopped, according to a U.N. statement said.
But the London-based Syrian Observatory for Human Rights, which documents anti-regime protests, said Thursday that Syrian troops had shot dead nine people in the central city of Homs on Wednesday night. Another rights group said Assad's crackdown also killed nine people elsewhere in Syria on Wednesday.
AP White House Correspondent Ben Feller contributed to this report.