The treaty, sealed after months of halting negotiation, is significant not just for what it does but for what it symbolizes: a fresh start for the United States and Russia, and evidence to a watching world that nuclear disarmament is more than a goal.
The pact commits their nations to slash the number of strategic nuclear warheads by one-third and more than halve the number of missiles, submarines and bombers carrying them.
That still leaves the two countries with enough nuclear firepower to ensure mutual destruction several times over, but the move sets a foundation for deeper reductions, which both sides are already pursuing.
"It sends a signal around the world that the United States and Russia are prepared to once again take leadership," Obama said moments after he and Medvedev signed the treaty in a gleaming, ornate hall in the Czech Republic's presidential castle.
Said the Russian president: "The entire world community has won."
The pact will shrink the limit of nuclear warheads to 1,550 per country over seven years, about a third less than the 2,200 currently permitted.
Looming over the celebration was Iran, which in the face of international pressures continues to assert that its uranium enrichment program is for peaceful purposes, not weapons. Six powers - the U.S., Russia, Britain, France, Germany and now China - are in talks in New York about a fourth set of United Nations sanctions to pressure Iran into compliance.
"We cannot turn a blind eye to this," Medvedev said in a show of solidarity. But he said he was frank with Obama about how far Russia was willing to go, favoring only what he called "smart" sanctions that might have hope of changing behavior.
Russia's Deputy Foreign Minister Sergei Ryabkov later elaborated by saying, for example, that Russia would not endorse a total embargo on the delivery of refined petroleum products into Iran. Such products might be targeted in other ways, or sanctions on Iran's energy sector might be avoided altogether to avoid running into deal-breaking opposition from Russia or China.
The nuclear arms pact now faces a ratification vote in the Russian legislature and the U.S. Senate. At home, Obama's team is struggling to get the required 67 votes, and the president himself is directly involved. He said he was confident that Democrats and Republicans would see that the treaty protects U.S. interests - an upbeat view of bipartisanship in a town where its been scarce.
"I feel confident that we are going to be able to get it ratified," Obama said.
Negotiations between the U.S. and Russia got bogged down in disputes, including Russia's objection to U.S. missile defense plans for Europe. The Kremlin is still concerned about the plan but sought to tamp down talk it would withdraw from the new treaty if there is a buildup in the missile defense system. Russia codified its option to withdraw in a statement in connection with the treaty.
Obama said the treaty itself built trust that would help in solving any differences on the issue. Responded Medvedev: "I am an optimist as well as my American colleague. I believe that we will be able to reach a compromise."
Beyond slashing nuclear arsenals, the U.S. sees the new "START" treaty, as it is known, as a key part of efforts to reset ties with Russia, badly strained under the Bush administration, and engage Moscow more in dealing with global challenges, including the nuclear arsenal of North Korea and nuclear ambitions of Iran.
The new pact is only part of the Obama administration's new nuclear strategy. It was signed only days after the White House announced a fundamental shift in its policy on the use of nuclear weapons, calling the acquisition of atomic arms by terrorists or rogue states a worse menace than the Cold War threat of mutual annihilation.
Other U.S. nuclear initiatives will follow the Prague signing. Leaders from more than 40 countries will gather in Washington next week to discuss improvements in securing nuclear materials.
The White House plans to lead calls for disarmament in May at the United Nations during an international conference on strengthening the Nuclear Nonproliferation Treaty.
The treaty signed Thursday is the most significant nuclear disarmament pact in a generation, and Medvedev has lauded it as "an important step" in disarmament and arms control efforts.
Russian analysts say Russia needs the deal to ease the burden of replacing a large number of aging Soviet-built missiles. "This treaty is in Russia's best interests," said Sergei Rogov, the head of the USA and Canada Institute, an influential think tank.
Inside the hall, the anticipated moment came as the two presidents picked up their pens, glanced at each other and grinned as they signed several documents, with aides transferring the papers back and forth so all would have both signatures. When it was done, the leaders seemed momentarily at a loss, with Medvedev flashing a smile and a shrug before they stood to shake hands.
While the Russian parliament is likely to follow the Kremlin's lead, the ratification process in the U.S. Senate could be troublesome. Fearing potential trouble, Moscow has said that Russian lawmakers will synchronize their moves to ratify the deal with the U.S. legislators.
Sensitive to East European concerns, Obama is tending to other business while in Prague - hosting a dinner for leaders from 11 Central and Eastern European nations formerly in or near Moscow's orbit, who worry about the Kremlin's post-communist push for influence.
Under Obama, Russian cooperation on key priorities, from helping to prevent a nuclear-armed Iran to opening supply routes for the U.S. military into Afghanistan and agreeing to new arms reductions, has increased - though not by a huge amount.
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Associated Press writer Vladimir Isachenkov contributed to this story.
