The measure now heads to the House of Representatives where its fate is uncertain.
But while passage in Senate late yesterday is a dramatic victory for Obama, the bill clearly faces a fierce debate in the lower chamber, where lawmakers signalled there is intense opposition from within Obama's own Democratic Party.
Passage of the so-called trade promotion authority bill allows the administration to finalise negotiations with 11 other Asian and Pacific nations and bring the trade deal to Congress for an up-or-down vote, with lawmakers not permitted to make changes.
TPA is "likely the most important bill we'll pass this year," said Senate Finance Committee chairman Orrin Hatch, who co-wrote the legislation that lays out 150 ambitious US trade priorities including human rights, environment and labor protections.
Obama offered swift praise for the result of the closely-watched vote.
He stressed that this TPA, previous versions of which were used by several presidents before him to conclude trade deals, includes "strong standards that will advance workers' rights, protect the environment, promote a free and open Internet, and it supports new robust measures to address unfair currency practices."
"The House will take up this measure, and Republicans will do our part, but ultimately success will require Democrats putting politics aside and doing what's best for the country," House Speaker John Boehner said after the Senate vote.
Many Democrats have argued that trade accords often result in sending American jobs to nations with low wages.
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