Thirteen Republicans broke with their top two leaders and joined 56 Democrats and two independents in providing the necessary two-thirds vote to approve the treaty. The vote was 71-26.
The accord, which still must be approved by Russia, would restart onsite weapons inspections as successors to President Ronald Reagan embraced his edict of "trust, but verify."
Vice President Joe Biden presided over the Senate and announced the vote. Secretary of State Hillary Rodham Clinton observed the vote from the Senate floor. Both had lobbied furiously for the treaty's approval.
"The question is whether we move the world a little out of the dark shadow of nuclear nightmare," Foreign Relations Committee Chairman John Kerry, D-Mass., said to his colleagues moments before the historic tally.
Calling the treaty a national security imperative, Obama had pressed for its approval before a new, more Republican Congress assumes power in January.
The Obama administration has argued that the United States must show credibility in its improved relations with its former Cold War foe, and the treaty was critical to any rapprochement. The White House is counting on Russia to help pressure Iran over its nuclear ambitions.
