The 60-to-38 vote on Wednesday clears the way for Obama to seek final language on a trade agreement with Japan and 10 other Pacific-rim nations. Congress can ratify or reject such agreements but not change them.
The Senate granted Obama the same fast-track authority that previous presidents have enjoyed. The GOP-controlled House passed it earlier with help from 28 Democrats.
The vote was a stinging defeat for environmental groups and for unions that say free-trade agreements kill U.S. jobs.
Obama and Republican leaders say U.S. producers must reach more global markets.