Susan Collins joined fellow moderate Republican senator Olympia Snowe, in endorsing the goal of far-reaching changes in the US health care system.
The proposals to overhaul of the $2.6 trillion (£1.6 trillion) system were passed by the Senate Finance Committee, setting the stage for a major battle on the Senate floor itself.
My hope is that we can fix the flaws in the bill and come together with a truly bipartisan bill that could garner widespread support," Mrs Collins said.
Democrats on the committee successfully persuaded Mrs Snowe of Maine to support the bill, giving Mr Obama a much-needed, if thin, cloak of bipartisanship for his reform push.She is the first Republican on Capitol Hill to break ranks by voting for the bill.
Under the compromise plan, $829 billion would be spent over the next decade to increase the proportion of insured Americans from 83 per cent to 94 per cent. Senator Max Baucus, the committee's Democratic chair, is assured of the votes to back the plan but the White House anxiously wants at least some Republican support.
The bill will be melded with a Senate Health Committee version before being debated in the full 100-member Senate, where Democrats will need all of their 60 votes to prevent a Republican filibuster.
In a sign of how the stakes are being raised on what is likely to be one of the defining issues of Mr Obama's four-year term, the White House was hitting back fiercely at the American insurance industry after claims that reform would add $1,700 (£1,075) to a typical health plan over the next four years.
The group America's Health Insurance Plans ended the insurance industry's uneasy truce with the White House and has not ruled out running attack advertisements against Mr Obama.
This has prompted a string of denunciations from the White House, Democrats and their allies, who described the group's analysis as "distorted and flawed", "fundamentally dishonest" and "a hatchet job".
Mrs Snowe was concerned about penalties in the bill for Americans who don't buy insurance. But even her "yes" vote appeared conditional - she hinted that she could vote yes in committee and no on the Senate floor.
“When history calls, history calls,” she said. “There are many, many miles to go in this legislative journey.
“My vote today is my vote today. It doesn’t forecast what it will be tomorrow.”
Republicans believe the Democratic reform measure will fuel an unacceptable increase in the national debt and undermine competition. Defeating Mr Obama on the issue also offers Republicans a prime opportunity to undermine his chances of re-election and Democratic hopes of solidifying their congressional majorities in next year's mid-term elections.
Mr Baucus, with White House support, has laboured for months to craft a compromise that would win over some Republicans. His bill, unlike the other one in the Senate and the three House of Representatives versions, does not involve setting up a government insurance plan.
While Mrs Snowe's rejection of the bill would probably not have prevented an eventual version being signed by Mr Obama, it would have seriously undermined his promise to bring a new bipartisanship to Washington.
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