After two brushes with failure, some fancy legislative footwork and myriad backroom deals to keep the legislation alive, lawmakers are expected to grant Obama the power to negotiate trade deals and send them on a fast track through Congress.
Approval could push negotiations on the 12-nation Trans-Pacific Partnership (TPP) over the finish line in time to get it through Congress before year-end. TPP is a central part of Obama's foreign policy pivot to Asia to counter the rising diplomatic and economic influence of China.
The deal, potentially a legacy-defining achievement for Obama, would create a free-trade zone stretching from Japan to Chile, comprising 40 per cent of the world economy and raising annual global economic output by nearly $300 billion.
The Senate voted 60-37 on Tuesday to clear a procedural path for a final vote on passage of fast-track authority, which would let lawmakers set negotiating goals for trade deals, including TPP, but restrict them to yes-or-no votes on final agreements.
The fast-track legislation itself now only needs a majority of votes to pass, a hurdle it cleared easily more than a month ago on its first run through the Senate.
It was forced back to the Senate floor after a revolt by House of Representatives Democrats resulted in fast-track being split from a companion measure extending a programme to help workers hurt by trade.
That bill now faces a separate vote in the Senate, as early as Wednesday, and another in the House. Republicans hope to pass that programme this week and send both measures to Obama for approval, before going on a week-long break.
The bruising congressional battle has pitted Obama against many in his own party, including House Democratic Leader Nancy Pelosi, and prompted blood-letting among Republicans after party leaders lashed out at conservatives who refused to back the trade agenda.
Although opinion polls show a majority of Americans support trade deals, congressional approval has been a tough slog because labour unions and liberal activists have campaigned against fast-track, warning of job losses and vowing to retaliate against Democrats who break ranks to support trade.
The front runner for the party's presidential nomination in the 2016, Hillary Clinton, said Democratic critics had legitimate concerns but has so far reserved judgment on the TPP, which could become an issue in 2016 election campaigns.
The TPP would be the biggest trade deal since the North American Free Trade Agreement 20 years ago between the United States, Canada and Mexico.
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