The Senate voted 50-48 in favour of the war powers resolution, which passed the House of Representatives early this month, reflecting growing concern even among some of Trump's Republicans about the unpopular conflict that began on February 28.
It was the first time both chambers of Congress had passed a resolution directing a president to remove US armed forces from hostilities since the War Powers Resolution, was enacted in 1973. While likely to remain largely symbolic, the vote was a setback for Trump, who until recently had enjoyed near-unanimous support from Republican members of Congress.
It also comes as the administration is expected to ask Congress to authorise tens of billions of dollars to pay for the war.
Trump's Republicans hold slim majorities in both the Senate and House, but a few have broken with the president on a handful of issues ahead of mid-term elections in November, which will determine whether the party will retain control of Congress.
The Senate vote was largely along party lines, with four Republicans joining all but one Democrat in favour. Two Republican senators did not vote.
Trump's administration is working to negotiate a peace agreement with Iran. Support for the resolution in Congress is likely to put pressure on the president not to resume hostilities, something he has suggested he might do if negotiations falter.
On Tuesday, a White House official said the Senate vote has no significance because the resolutions do not go to the president and have no force of law and the measure passed only because two Republicans were absent.
The official also said the resolution directs Trump to remove US forces from hostilities, which the White House says were terminated with a ceasefire on April 7. Experts say the constitutionality of the War Powers Act likely will be settled in the courts.
Representative Gregory Meeks of New York, who sponsored the resolution in the House, said he viewed the resolution as binding and would pursue all legal avenues to ensure that the administration complies.
Democrats also noted the US Constitution gives Congress, not the president, the right to take the country to war.
"Congress has to own this responsibility," Democratic Senator Tim Kaine of Virginia said in a speech urging support for the measure.
The resolution had also passed the House with slim Republican support. The tally there was 215-208 with four Republicans and every Democrat voting in favour.
Democratic politicians have promised additional votes on war powers measures, saying they want to force Republicans to go on the record about the war.
Senate Republican Majority Leader John Thune of South Dakota said he expected Congress would review and vote on an eventual Iran peace deal.
