Osama Bin Laden's swift dispatch sent a deadly warning to Taliban leaders to throw in the towel - or face a similar fate.
"Our message to the Taliban remains the same, but today it may have even greater resonance - you cannot wait us out, you cannot defeat us," Secretary of State Clinton said.
The time for Taliban deal-making with the Afghan government was running short, Clinton said, "but you can make the choice to abandon Al Qaeda and participate in a peaceful political process."
With White House backing, but scant support from the Pentagon, Clinton has been pressing for a diplomatic settlement ahead of the July start of U.S. troop withdrawals.
The elimination of Bin Laden could complicate Clinton's strategy.
"Osama Bin Laden's death means that President Obama will likely face increased pressure to withdraw U.S. troops from Afghanistan sooner rather than later," said Nora Bensahel of the Center for a New American Security.
Other analysts warned of a possible backlash in the form of terror attacks on Americans at home and abroad.
"We have to be prepared," said Richard Haas, president of the Council on Foreign Relations. Yet he added that Bin Laden's kill shot serves as a reminder to other terror kingpins that "what goes around can come around."
The raid on Bin Laden's well-appointed compound far from Al Qaeda safe havens near the Afghan border also threw the troubled U.S. relationship with Pakistan into more disarray.
The White House and the Pentagon portrayed the raid as a solo success of American stealth that was pulled off under the noses of Pakistan's military and intelligence services.
Clinton emerged from the State Department twice to speak of Pakistani "cooperation."
"Cooperation with Pakistan helped lead us to Bin Laden and the compound in which he was hiding," she said.
The friction between the two governments was overplayed for political ends by both sides, a well-placed Pakistani source said. "There is an agreement between our governments," the source said, "but no one acknowledges it because they can't."
The raid was "a violation of sovereignty, so they can't say, 'Invade our country and come shoot from our skies,'" the source added.
Sen. Chuck Schumer (D-N.Y.) brushed aside the diplomatic subtleties, insisting the raid "marked a turning point in the U.S. war on terror."