WASHINGTON — The Senate voted on Saturday to begin full debate on major health care legislation, propelling President Obama’s top domestic initiative over a crucial, preliminary hurdle in a formidable display of muscle-flexing by the Democratic majority.

“Tonight we have the opportunity, the historic opportunity to reform health care once and for all,” said Senator Max Baucus, Democrat of Montana, and a chief architect of the legislation. “History is knocking on the door. Let’s open it. Let’s begin the debate.”

The 60-to-39 vote, along party lines, clears the way for weeks of rowdy floor proceedings that will begin after Thanksgiving and last through much of December.

The Senate bill seeks to extend health benefits to roughly 31 million Americans who are now uninsured, at a cost of $848 billion over 10 years.

The House earlier this month approved its health care bill by 220 to 215, with just one Republican voting in favor. That measure is broadly similar to the Senate legislation, but there are some major differences that would have to be resolved before a bill could reach Mr. Obama, and that would almost surely push the process into next year.

As the Democrats succeeded Saturday in uniting their caucus by winning over the last two holdouts, big disagreements remained, making final approval of the bill far from certain.

Two reluctant Democratic senators, Mary L. Landrieu of Louisiana and Blanche Lincoln of Arkansas, warned that their support for a motion to open debate did not guarantee that they would ultimately vote for the bill. Their remarks echoed previous comments by several other senators, including Ben Nelson, Democrat of Nebraska, and Joseph I. Lieberman, independent of Connecticut.

Those comments made clear that more horse-trading lies ahead and that major changes might be required if the bill is to be approved. And it suggested that the Senate majority leader, Harry Reid of Nevada, who relied only on members aligned with his party to bring the bill to the floor, may yet have to sway one or more Republicans to his side to get the bill adopted.

The Senate Republican leader, Mitch McConnell of Kentucky, said his party’s opposition would persist. “The battle has just begun,” he said.

In a rare ceremonial gesture reserved for major votes, senators cast their yeas and nays from their desks in the chamber, each one rising to voice his or her position. Senator George V. Voinovich, Republican of Ohio, was not present and did not vote.

After the vote, Mr. Reid said he understood that Ms. Landrieu was already working with two other Democratic senators, Thomas R. Carper of Delaware and Charles E. Schumer of New York, to see if they could devise a public insurance plan with broad appeal.

The White House issued a statement praising the vote. “The President is gratified that the Senate has acted to begin consideration of health insurance reform legislation,” his press secretary, Robert Gibbs, said, adding that President Obama “looks forward to a thorough and productive debate.”

Mrs. Lincoln, who faces a tough re-election campaign next year and has in recent weeks been the target of millions of dollars in television advertising by both sides in the health care fight, said pointedly that she would not vote for the measure if it retained a government-run health insurance plan, known as the public option, to compete with private insurers. “Although I don’t agree with everything in this bill, I believe it is more important that we begin debate on how to improve the health care system for all Americans,” said Mrs. Lincoln, who was the last uncommitted Democrat, and whose speech, at about 2:30 p.m. Saturday, lifted a cloud of suspense that had hovered around the Capitol.

She added: “But let me be perfectly clear. I am opposed to a new government-administered health care plan as a part of comprehensive health insurance reform, and I will not vote in favor of the proposal that has been introduced by leader Reid as it is written.” But Senator Lieberman, who voted to take up the health care bill, said he was still staunchly opposed to a government-run plan. It is “a terrible idea,” he said.

Ms. Landrieu, whose support came after she won a provision that could be worth more than $100 million in additional federal aid for her financially troubled state, said, “I have decided there are enough significant reforms and safeguards in this bill to move forward, but much more work needs to be done.”

A parade of Democrats and Republicans spent Saturday laying out their arguments for and against the bill in floor speeches.

Mr. Reid, in a rousing closing speech given at his customary volume, which is barely audible, likened the health care bill to some of the most profound issues confronted by the Senate across history.

“Imagine if instead of debating either of the historic G.I. Bills — legislation that has given so many brave Americans the chance to brave college — if this body had stood silent,” Mr. Reid said. “Imagine if instead of debating the bills that created Social Security or Medicare, the Senate’s voices had been stilled. Imagine if instead of debating whether to abolish slavery, instead of debating whether giving women and minorities a right to vote, those who disagreed were muted, discussion was killed.”

With the Democrats nominally controlling 60 votes — the precise number needed to overcome the Republican attempt to stop the bill — the vote on Saturday evening was the biggest test yet of the Democrats’ resolve and of Mr. Reid’s ability to unite his fragile caucus. Mr. Reid faces a tough re-election fight next year.

The bill would expand health benefits by broadly expanding Medicaid, the federal-state insurance program for low-income people, and by providing subsidies to help moderate-income people buy either private insurance or coverage under a new government-run plan, the public option. And it would impose a requirement that nearly all Americans obtain insurance or pay monetary penalties for failing to do so.

According to the Congressional Budget Office, the cost of the legislation would be more than offset by new taxes and fees and reductions in government spending, so that the bill would reduce future federal budget deficits by $130 billion through 2019.

Mr. Reid accused Republicans who opposed the legislation of "living in a different world." He and several other Democrats also used their speeches to assail perceived abuses by private insurers. "The health insurance industry has an insatiable appetite for more profit," Mr. Reid said.

Senate Republicans countered with an impassioned denunciation of the measure as an ill-conceived budget-busting expansion of government and a threat to the health and economic security of all Americans, especially the elderly.

The Republicans sought to portray the vote on Saturday — on whether to end debate on a motion to bring up the health bill — as tantamount to a vote on the bill itself, and to shake the confidence of Democrats who had wavered in recent days.

In his closing argument, just ahead of the vote, Mr. McConnell implored at least a single Democrat to vote no. "If we don't stop this bill tonight," he said, "the only debate we'll be having is about higher premiums, not savings for the American people, higher taxes instead of lower costs, and cuts to Medicare rather than improving seniors' care."

"The American people are looking at the Senate tonight; they're hoping we say no to this bill," Mr. McConnell added moments later, holding up a single index finger. "All it would take," he said, "is just one member of the other side of the aisle, just one, to give us an opportunity not to end the debate but to change the debate in the direction the American people would like us to go."

Mr. McConnell warned of the political consequences for senators who voted to move ahead. "Senators who support this bill have a lot of explaining to do," he said. "Americans know that a vote to proceed on this bill, to get on this bill, is a vote for higher premiums, higher taxes and massive cuts to Medicare."

Republicans also said that the vote was a proxy for a larger dispute over abortion, because they said the bill did not sufficiently restrict the use of federal money for insurance covering abortions. Senator Mike Johanns, Republican of Nebraska, described the vote as "the key vote on abortion in the health care debate."

Saturday night's vote was required because Senate rules and precedent have long granted a right of virtually unlimited debate, or filibuster, to the minority that can be curtailed only by a supermajority vote of 60 senators to move ahead. Currently, there are 58 Democrats in the Senate and two independents who routinely align with them. If the Democrats had lost the vote, they could have tried again, presumably after changing the bill to try to attract more votes.

Senator Patrick J. Leahy, Democrat of Vermont assailed the Republicans as obstructionists on Saturday morning. "I will vote today to end the filibuster so the Senate can begin the historic debate to improve and reform our nation's health insurance system," he said. "Let's not duck the debate, let the debate begin. Let's not hide from the votes."

While Democrats generally agree on the broad goals of the legislation, to cover the uninsured and to slow the growth in health care spending, there are potentially serious disagreements over any number of provisions that could sink the bill.

Ms. Landrieu, in her speech, methodically cataloged provisions of the bill that she liked and those that she said needed improvement.

Under the bill, she said, owners of small businesses would no longer face "volatile costs" for health insurance. In addition, she said, the bill would "encourage employers to move away from high-cost benefit plans" and shift some compensation to wages.

But more needed to be done to improve the bill, she argued, particularly to help small businesses and the self-employed. And she issued a stern warning about the public option, one of the most contentious features of the sweeping health care legislation.