WASHINGTON (Reuters) —A sweeping health care overhaul narrowly cleared its first hurdle in the Senate on Saturday, with Democrats casting 60 party-line votes to open debate on the biggest health care changes in decades.

In the first Senate test for President Barack Obama's top domestic priority, Democrats unanimously backed a procedural motion to open debate over the opposition of 39 Republicans. Sen. George Voinovich, R-Ohio, did not vote.

Democrats needed 60 votes to approve the motion in the 100-member Senate and had no margin for error—they control exactly 60 votes.

The Democratic victory was assured earlier in the day when the party's last two holdouts, Sen. Blanche Lincoln, D-Ark., and Sen. Mary Landrieu, d-La., said they would support the motion but would not commit to backing the final bill without changes.

“I believe that it is more important that we begin this debate to improve our nation's health care system for all Americans rather than just simply drop the issue and walk away,” Sen. Lincoln said in a speech hours before the vote.

The debate will begin on Nov. 30 and is expected to last at least three weeks. The House of Representatives has passed its own version, and differences in the two would have to be reconciled in January before President Obama could sign a final measure.

The health care reform bill would expand coverage to millions of uninsured and bar insurance practices like denying coverage to those with pre-existing conditions.

The legislation would spark the biggest changes in the $2.5 trillion health care system—which accounts for one-sixth of the U.S. economy—since the 1965 creation of the Medicare government health insurance plan for the elderly.

The stakes are high for President Obama, with his political standing and legislative agenda on the line less than a year into his first term. White House spokesman Robert Gibbs said Mr. Obama was gratified by the vote and “looks forward to a thorough and productive debate.”

During a formal roll call, senators sat at their desks and called out their votes as their names were read. Visitors in the galleries cheered when the final tally was announced.

The health care overhaul still faces significant challenges, with Senate majority leader Harry Reid, D-Nev., trying to accommodate competing views in his party on issues like abortion, a government-run insurance plan and efforts to rein in costs.

Republicans also have vowed to delay or block the bill, which they condemned as a costly government intrusion in the private sector that would raise insurance premiums, reduce consumer choices and raise taxes.

“The health care debate is now officially under way on this 2,074 page, multi-trillion-dollar health care experiment,” Senate minority leader Mitch McConnell, R-Ky., said.

Sen. McConnell said the final Democratic holdouts had to “twist themselves into a pretzel” to justify voting to move ahead on the bill. Almost all Senate bills that clear the first hurdle eventually pass, he said.

“The easiest time to change this bill, if you were serious about it, is right now,” Sen. McConnell told reporters. “The time of maximum leverage would have been before tonight's vote.”

Senators Landrieu and Lincoln, moderates from conservative Southern states where the overhaul is unpopular, said they simply wanted the debate to begin so they could work for more changes.

Sen. Lincoln, who faces a tough re-election battle next year, said she opposes the government-run insurance option included in the bill and will not vote for final passage if it remains.

“I'm not thinking about my re-election, the legacy of a president or whether Democrats or Republicans are going to be able to claim victory,” she said.

Sen. Landrieu said she wanted to change the bill to make health care more affordable, ease the burden on small businesses and rein in the growth of costs.

“There are enough significant reforms and safeguards in this bill to move forward, but much more work needs to be done before I can support this effort,” Landrieu said.

Senators Landrieu and Lincoln had been showered with attention by Sen. Reid and Obama administration officials as they pondered their vote.

In her Senate floor speech, Sen. Landrieu defended her successful effort to win more funds in the bill for Medicaid, the government health program for the poor, for her home state of Louisiana.

“I am proud to have fought for it,” she said. “But that is not the reason I am moving to debate.”

The Senate bill would require virtually all Americans to buy insurance and would set up exchanges where they could choose among various options. It would offer subsidies to help low-income workers pay for the coverage.

Republicans have criticized its tax increases to help pay for the expanded insurance coverage. It would also raise the Medicare payroll tax on high-income workers, which is used to finance Medicare, and impose a tax on high-cost “Cadillac” insurance plans.