Rand Paul of Kentucky and Mike Lee of Utah, both Republicans, were the only votes against it - bolsters existing sanctions and would allow Congress to thwart any presidential effort to curtail sanctions without congressional approval.
So far, at least, that has been a bet worth taking for the White House, though the new penalties against Russian Federation are also built into a bill that gives Trump something he wants: new sanctions on Iran - so that raises the stakes for the president should he threaten a veto.
The Senate-passed sanctions bill also converts existing penalties against Moscow into law, potentially making them more hard to remove, and prevents the Trump administration from returning two Russian diplomatic compounds seized in December by the Obama administration as punishment for alleged electoral disruption.
If signed into law, the document would prohibit the USA president from being able to lift sanctions without Congressional approval. It also establishes new sanctions against those conducting cyberattacks on behalf of the Russian government as well as supplying arms to Syrian President Bashar Assad, and it allows for sanctions to hit Russia's mining, metals, shipping and railways sectors.
The bill, imposing another round of sanctions on Russian Federation, was passed in a 97-2 vote on Wednesday and is yet to be considered by the House of Representatives.
Some of the sanctions were originally proposed by Barack Obama's administration, while others are new, but they are all meant to punish the Russian government for what USA intelligence agencies say was an effort to damage Democratic nominee Hillary Clinton by leaking embarrassing emails. Testifying this week on Capitol Hill, Secretary of State Rex Tillerson acknowledged the need to take action against Russian Federation but warned against measures that would cut off dialogue with Moscow.
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It remained unknown whether Trump, who had been seeking rapprochement with Russian Federation for months, would sign the bill into law.
The Russia sanctions measure was added as an amendment to an Iranian sanctions bill, after a deal was struck between the heads of the Senate Foreign Relations and Banking Committees.
The Senate also passed two amendments before approving the bill.
In another challenge to Trump's foreign policy, the measure also "reaffirm the strategic importance" of North Atlantic Treaty Organisation.