Senators voted by 14 votes to nine to pass the bill, with one Republican joining Democrats on the Senate Finance Committee in voting in favour.
Senator Olympia Snowe became the first Republican to back the proposals.
The reforms, intended to cut costs and make insurance more affordable, are Mr Obama's top domestic priority.
The president welcomed the committee's decision, calling it a "critical milestone".
"We are closer than ever before to passing healthcare reform but we are not there yet," he said. "Now is not the time to pat ourselves on the back... It is time to dig in further and get this done."
'Miles to go'
Obama welcomed the progress made so far on the billAnnouncing her decision to break with her party on Tuesday, Senator Snowe said: "When history calls, history calls."
However, the moderate Republican said it did not necessarily mean she would support later versions of a bill.
"There are many, many miles to go in this legislative journey," she said. "My vote today is my vote today. It doesn't forecast what it will be tomorrow."
The panel's bill, which was drafted after weeks of at times bitterly bipartisan debate, sets out a 10-year $829bn (£525bn) plan to cut health costs and provide affordable health insurance to most Americans.
US HEALTHCARE No universal coveragePrivate health insurance available through employer, government or private schemesUS spends some 16.2% of GDP on healthcare, nearly twice average of other OECD countriesUS Census Bureau estimates some 46m people do not have health insurance - includes 9.2 million non-citizens and 18 million people who earn over $50,000 a yearMedicaid: federal-state programme for low income groupsMedicare: for people 65 years old and above and some younger disabled people
Q&A: Healthcare reform Healthcare around world Senator Charles Grassley, the senior Republican on the panel, criticised the legislation and predicted that the bill would move "leftward" as it progressed through Congress.
"This bill is already moving on a slippery slope to more government control of healthcare," he said.
The finance committee's bill must now be combined with a bill drafted by the Senate Health Committee before going to the full Senate for a vote.
It is not guaranteed to pass, as it needs all the Democrats, two independents and one Republican to vote in favour.
Mr Obama argues that all Americans are entitled to insurance coverage, that rising costs must be tackled and that private insurers must not be able to deny coverage or end it when someone becomes seriously ill.
ANALYSIS Paul Adams, BBC News, WashingtonOn the long, tortuous road towards reform of America's healthcare system, this was a decisive moment. Several members of the Senate Finance Committee called the vote historic. The Washington Post this morning reported that not since Theodore Roosevelt proposed universal healthcare in 1912 has any such bill come this far. After months of debate, the committee's chairman, Max Baucus, looked delighted and relieved. In the end, those in favour of the bill won comfortably. This was due in part to a Democratic majority, but also to the support of Senator Olympia Snowe, who became the first Republican to back any of the bills proposed this year.
But this is not the end of the process. There are many more legislative hurdles to overcome before it becomes law. In the meantime, debate will continue to rage. A long congressional slog still lies ahead, correspondents say, but Mr Obama's push for healthcare reform has gone further than attempts in the 1990s by President Bill Clinton, which never got beyond all the committees.
All the different versions of the bill produced by House of Representatives and Senate committees are broadly similar in the scope of their reforms:
toughen regulations on health insurers mandate all Americans to get insurance offer subsidies to the less well-off and set up health insurance exchanges for people without employer-sponsored coverage, to help them choose between different options. Lawmakers are divided, however, over whether there should be a new government-run insurance scheme - the so-called "public option".
The finance committee's bill is the only one not to include a public option, an element advocated by Mr Obama and some Democrats as the means of creating competition between insurers.
Last week, the nonpartisan Congressional Budget Office concluded that the finance committee's bill would result in reducing the federal deficit by $81bn and mean some 94% of eligible Americans would have insurance coverage.
However, Republicans say the final draft which will be voted on is likely to be very different and more expensive than this version. They say the proposed reforms are too costly and represent too much government intrusion into healthcare.
At the weekend, the private insurance industry issued a study that said the plans could mean policies end up costing people hundreds, if not thousands, more dollars.