The Obama administration will be compelled to shift roles - from managing a volatile political standoff that paralyzed a regional ally to ensuring that Egypt's commanding generals, many of them trained in the United States, carry out the political and legal changes necessary to guarantee fair elections later this year.
"This is not the end of Egypt's transition," Obama said Friday at the White House. "It is the beginning."
Mubarak's resignation ignited celebrations across the Arab Middle East, including festive gunfire in Lebanon and joyous demonstrations in the West Bank city of Ramallah. But in Israel, where government officials watched anxiously as one of the country's few Arab partners retreated to a Red Sea resort, the sentiment was one of apprehension about whether Egypt's revolution could mean further isolation for the Jewish state.
The Obama administration is already looking beyond Cairo, just as it quickly turned the page on Tunis after President Zine el-Abidine Ben Ali fled amid public protest a month ago, to the monarchies of Saudi Arabia and Jordan.
Senior U.S. officials say the economic stagnation, youthful populations and simmering political frustration in those kingdoms - echoes of Tunis and Cairo - may provide the spark for widespread political change that could usher out allies in favor of angry, anti-Western opposition movements. How to encourage the election of governments that are responsive to their electorates and to U.S. interests remains a challenge.
Ben Rhodes, the deputy national security adviser for strategic communication, said the administration had reached out by phone to officials across the Arab world in recent days to assure them that the United States intends "to keep its commitments."
"In addition to that message of reassurance, we've also been clear, publicly and privately, that the best antidote to protest is reform that opens up societies," Rhodes said.
But a senior Republican member of Congress who has access to intelligence reports said U.S. spy agencies have seen recent indications that other Middle East leaders were dismayed by the United States' treatment of Mubarak.
"The other countries are mad as hell, and they're mad as hell at us," said the lawmaker, who spoke on the condition of anonymity to discuss the matter candidly.
Emerging from the secular nationalist movement that produced Gamal Abdel Nasser and Anwar Sadat, Mubarak presented five U.S. presidents with a choice: push for greater democracy in a bellwether nation that gave birth to modern political Islam or tolerate repression in order to promote regional stability and support an Arab government willing to offer Israel at least a tepid partnership.
For decades, the U.S. government chose the latter path, a record that could turn the democratic process that may emerge from Cairo's Tahrir Square against the United States. The posture of key opposition groups such as the Muslim Brotherhood, whose opposition to Israel endures, is also likely to shape whatever replaces Mubarak's government.
Mubarak leaves behind the rigid institutions and laws of a police state, including the emergency decree he used to suspend many civil liberties, and a powerful army with a large stake in who leads the country. Egypt's Armed Forces Supreme Council announced Friday that it is in command, at least temporarily.
"Obama's insistence that this was about how Egypt is governed, not who governs Egypt, which was awkward for him, is actually the right thing to be insisting on now that Mubarak is gone," said Tom Malinowski, the Washington director of Human Rights Watch and one of several outside advisers the White House assembled in recent weeks to consult on Egypt. "It will be inspiring for opposition movements, but also potentially something that causes governments to crack down harder."
Senate Foreign Relations Chairman John F. Kerry (D-Mass.) said, "I don't think anybody should be getting too carried away with a victory lap today."
"You have a military in charge that has yet to prove it knows how to manage this kind of transition," he said. Mubarak's example may make the region's unelected leaders, especially those supported by the United States, more willing to adopt political reforms before public protest sweeps them away as well, he said.
"The question is how do they respond and we need to work with them on how to do so," Kerry said. "This is the challenge of the Middle East."
Administration officials point to the 1979 Iranian revolution and the 1998 uprising against Indonesian President Suharto as examples of street protests overturning U.S.-backed dictatorships, expressing the hope that the turmoil in Egypt eventually yields a democracy similar to Indonesia's. That outcome is vastly superior, in American eyes, to the rule of the clerics that has emerged in Iran.
The increasing political volatility in the region has large implications for U.S. security interests, and some of the most vulnerable countries are important in different ways.
The aging monarchy of Saudi Arabia, home to roughly a fifth of the world's proven oil reserves, governs a population where many are influenced by the most extreme interpretation of Islam, one hostile to Western culture.
The cosmopolitan Saudi elite fear the majority and have accepted the Sauds as an alternative to a more severe Islamist government. How the octogenarian leadership would weather a popular uprising is unclear.
In Jordan, King Abdullah II has fired his government and taken steps to appease public anger fanned by the uprisings in Egypt and Tunisia.
Sandwiched between a fragile Iraq and the volatile Palestinian territories, Jordan has been a pro-Western oasis for years, often over the objection of population includes majority of Palestinian descent and a large Iraqi diaspora.
And in Yemen, where demonstrators have taken to the streets against President Ali Abdullah Saleh, the Obama administration is carrying out counterterrorism operations in secret partnership with the government.
"We do have mending to do with the Saudis and others, who seem to have concluded we threw Mubarak over the side," said Elliott Abrams, a former deputy national security adviser for the Middle East under George W. Bush. "It will take a little tending to the relationship with the king and possibly with others."
Abrams, who has been advising the Obama administration on Egypt in recent weeks, said "we come out of this as a country in pretty good shape, with a basis to build a relationship with the new government. "
Staff writers Greg Miller and Mary Beth Sheridan contributed to this report.