Vice President Joe Biden said the developments in Cairo and elsewhere mark a day of "historic" and "dramatic" change. It is a "pivotal moment in history" after which the future of Egypt -- a critical U.S. ally in the Middle East -- will be determined by its people, he said.
The U.S. government will continue to insist on a "set of core principles" in the months ahead, the vice president told an audience in Kentucky. Violence and intimidation against protesters remains unacceptable, he said. The universal rights of people "must be respected" and their "aspirations met."
Finally, he said, the transition must be "irreversible" and part of a negotiated path to democracy.
"The United States has largely spoken with one voice," on the Egyptian revolution and needs to remain politically united in responding to the change, Biden concluded.
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Obama was in a meeting in the Oval Office when he learned that Mubarak was stepping down, said Tommy Vietor, a spokesman for the National Security Council. Obama watched television coverage of the events in Egypt for several minutes afterward, Vietor said.
Obama did not talk to Mubarak or Egyptian Vice President Omar Suleiman before the announcement of Mubarak's resignation, according to White House Press Secretary Robert Gibbs.
Moments after the news broke, Senate Majority Leader Harry Reid, D-Nevada, issued a statement urging a peaceful transition.
"I am pleased that President Mubarak has heard and heeded the voice of the Egyptian people, who have called for change," Reid said. But "it is crucial that Mubarak's departure be an orderly one and that it leads to true democracy for Egypt, including free, fair and open elections."
He added, "We caution all sides against violence during this transition."
Senate Foreign Relations Committee Chairman John Kerry, D-Massachusetts, released a statement calling Mubarak's resignation "an extraordinary moment for Egypt."
But "what happens next will have repercussions far beyond Egypt's borders," he said. "We know from recent experience in Gaza that this requires not just elections, but hard work to build a government that is transparent, accountable, and broadly representative."'
Mubarak's decision to step down is "obviously a welcome step," a U.S. official involved in the Egypt discussions said earlier. But now comes "an unpredictable next chapter."
The official said CNN Mubarak's decision was "a sign the (Egyptian) military chose society" over the country's longtime ruler.
U.S. defense officials were not given any advance warning of Mubarak's resignation and were not sure it would happen.
As the Obama administration began to react, Washington was using a variety of intelligence assets to see what was happening in Cairo and other Egyptian cities, CNN has learned.
The U.S. military and intelligence community are using "national technical means" in the sky over Egypt to gather information about the demonstrations and the deployment of Egyptian security forces.
The phrase "national technical means" is used by the U.S. government to generally refer to the use of reconnaissance satellites to gather imagery or signals intelligence.
A senior U.S. official with direct knowledge of the operation confirmed the intelligence gathering, but declined to be identified because of the sensitive nature of the matter.
The official declined to say to what extent the Egyptian government is aware of the activity. The official would not say specifically which intelligence-gathering elements were being used, but indicated operations were being conducted in a manner that would not be visible to the Egyptian populace.
The official said the decision to use intelligence-gathering assets came in part after the initial violence erupted in the early days of the Cairo demonstrations.