The future of Obamacare looks bleaker after Senators narrowly voted to begin discussions of repealing and replacing the bill.
Republican John McCain, recently diagnosed with a brain tumour, cast one of the decisive ballots as the vote finished 51 to 50 in favour.
No Democrats voted in favour of opening the repeal debate.
Donald Trump, who campaigned vociferously in favour of scrapping Obamacare during his presidential election campaign, praised the Senate for moving forward on health care reform.
The Senate will now open up discussions over what the Affordable Care Act (ACA), passed under Barack Obama in 2010, could be replaced with.
Speaking during a press conference on Tuesday, President Trump said the successful vote represented a "big step".
Despite being a crucial move forward for the president, the victory now sparks a week-long debate over healthcare.
The incredibly narrow margin of victory also highlighted the divide in opinion over healthcare among members of the Republican party.
Repeating his frequent disdain of the ACA, President Trump told reporters following the vote that Obamacare should have been "terminated long ago".
The Republican said the bill had been a "disaster" for the US.
"Now we move forward towards truly great healthcare for the American people. We look forward to that. This was a big step," he said.
Ahead of voting, demonstrators interrupted the start of the crucial vote, with shouts of "kill that bill, don't kill us" and "shame" as they stood in the visitors' gallery.