Seven Republicans broke with Trump to support the resolution, which was co-sponsored by Sens. Bernie Sanders, I-Vt. and Mike Lee, R-Utah. They were: Lee, Susan Collins of Maine, Steve Daines of Montana, Jerry Moran of Kansas, Lisa Murkowski of Alaska, Rand Paul of Kentucky and Todd Young of Indiana.
Lawmakers have never before invoked the War Powers Resolution of 1973 to stop a foreign conflict, but Wednesday's 54-46 vote brought them a step closer to doing just that in order to cut off U.S. support for a war that has triggered a humanitarian catastrophe.
"The bottom line is that the United States should not be supporting a catastrophic war led by a despotic regime with an irresponsible foreign policy," Sanders said on Wednesday from the Senate floor. He said a vote in favor of the measure would "begin the process of reclaiming our constitutional authority by ending United States involvement in a war that has not been authorized by Congress and is unconstitutional."
The measure will move to the Democrat-controlled House, where it is expected to pass. Trump has threatened to veto the resolution, which the White House says raises "serious constitutional concerns."
In its statement threatening a veto, the White House argued that the premise of the resolution is flawed, and that it would undermine the fight against extremism. U.S. support for the Saudis does not constitute engaging in "hostilities," the statement said, and the Yemen resolution "seeks to override the president's determination as commander in chief."
"By defining `hostilities' to include defense cooperation such as aerial refueling," the White House statement said, the Yemen resolution could also "establish bad precedent for future legislation."
Trump's support for Saudi Arabia has been a point of tension with Congress since the killing of U.S.-based activist and writer Jamal Khashoggi last year. Lawmakers from both parties have criticized Trump for not condemning Saudi Arabia strongly enough for the killing.
Sen. Majority Leader Mitch McConnell, R-Ky., addressed those tensions when he urged his colleagues to oppose the measure.
"We should not use this specific vote on a specific policy decision as some proxy for all the Senate's broad feelings about foreign affairs. Concerns about Saudi human rights issues should be directly addressed with the administration and with Saudi officials," McConnell said from the Senate floor.
McConnell argued that the Yemen resolution would "not enhance America's diplomatic leverage" and would make it more difficult for the U.S. to help end the conflict in Yemen and minimize civilian casualties.
Sen. James Risch, R-Idaho, who chairs the Foreign Relations Committee, argued that U.S. support for the Saudi-led coalition helps facilitate peace talks and withdrawing from the conflict would delay an eventual political settlement.
"Peace envoys are telling us they want deeper U.S. engagement in this situation," Risch said in a statement following the vote. "This resolution sends a terrible message of U.S. division and lack of resolve, and sets a bad precedent for using the War Powers Resolution to express political disagreements with a president. We should instead signal our resolve that the U.S. is committed to playing an important role in pushing for a sustainable political settlement in Yemen."
A similar resolution to end support for the Yemen war passed the Senate in December, but it was not taken up by the House, which was then controlled by Republicans.
Approaching its fifth year, the war in Yemen has killed thousands and left millions on the brink of starvation, creating what the United Nations called the world's worst humanitarian crisis.
Sen. Chris Murphy, D-Conn., said before the vote that the resolution "will be seen as a message to the Saudis that they need to clean up their act."
"We are made weaker in the eyes of the world when we willingly participate in war crimes, when we allow our partners to engage in the slaughter of innocents," Murphy said.
Fox News' Chad Pergram and The Associated Press contributed to this report.