WASHINGTON — The Senate took a major step early Wednesday toward enacting a vast expansion of the nation’s social safety net, approving a $3.5 trillion budget blueprint along party lines that would allow Democrats to tackle climate change, and fund health care, child care, family leave and public education expansion while increasing taxes on wealthy people and corporations.

After an unusual bipartisan approval of a $1 trillion infrastructure package a day earlier, the vote over unanimous Republican opposition allows Senate Democrats this fall to create an expansive package that will carry the remainder of President Joe Biden’s $4 trillion economic agenda. The Senate adopted the measure 50-49, with one lawmaker, Sen. Mike Rounds, R-S.D., absent.

The blueprint sets in motion a perilous legislative process aimed at creating the largest expansion of the federal safety net in nearly six decades. The House will return early from its scheduled summer recess the week of Aug. 23 to take up the budget, so committees in both chambers can begin work fleshing out the party’s vision for what would be the greatest change to social welfare since the 1960s’ Great Society.

But Democratic unity just before the crack of dawn Wednesday could belie difficulties ahead. Sens. Joe Manchin of West Virginia and Kyrsten Sinema of Arizona, the Senate’s most vocal moderate Democrats, said they voted for the budget blueprint to keep to process moving, but they have pointedly indicated they may not support the expansive legislation that the budget vote protects from a Republican filibuster.

Hours after the legislation cleared the Senate, Manchin issued a statement outlining “serious concerns about the grave consequences facing West Virginians and every American family if Congress decides to spend another $3.5 trillion.”

A single Democratic defection would doom the effort. So the party’s progressive and moderate wings will have to hold together against united Republican opposition. House Democratic leaders planned a conference call Wednesday to try to bring their divided caucus together.

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The budget blueprint’s passage came after a marathon session of rapid-fire votes. Republicans, powerless to stop the measure in a Senate that Democrats control with Vice President Kamala Harris’ tiebreaking vote, pelted Democrats with politically freighted amendments. The votes dragged deep into the night for more than 14 hours before Democrats muscled through the measure minutes before 4 a.m., breaking into scattered applause.

“This legislation will not only provide enormous support to the kids of this country, to the parents of this country, to the elderly people of this country,” said Sen. Bernie Sanders, I-Vt., who is in charge of the Budget Committee. “But it will also, I hope, restore the belief that in America we can have a government that works for all, not just the few.”

Republicans denounced the measure as a launchpad for an unparalleled wave of spending that could ruin the country’s finances and its economy.

“People want to pretend this is just business as usual — just liberals doing liberal things using Senate procedure,” said Sen. Mitch McConnell, R-Ky., the minority leader. “Make no mistake. This reckless taxing and spending spree is like nothing we’ve seen.”

Moderate Democrats have also expressed qualms. They are agitating for a quick vote on the bipartisan infrastructure package, before consideration of the social policy bill. Progressives say they will not vote on the infrastructure bill until the Senate approves the full social policy package, fearing that if the infrastructure bill is signed into law, moderate Democrats will declare victory and withdraw support for the liberals’ priority bill.

“Democrats have labored for months to reach this point, and there are many labors to come,” said Sen. Chuck Schumer, D-N.Y., the majority leader. “But I can say with absolute certainty that it will be worth doing.”

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The budget resolution will ultimately allow Democrats to use the fast-track budget reconciliation process to shield the legislation from a Republican filibuster. It will pave the way to expand Medicare to include dental, health and vision benefits, and possibly to lower the program’s eligibility age from 65; fund a host of climate change programs; provide free prekindergarten and community college; create a paid family and medical leave program; and levy higher taxes on wealthy businesses and corporations.

Many liberals in both chambers have sought even more spending, and said this week they will not accept a package below $3.5 trillion.

Senate Republicans sought to exploit Democratic divisions through the so-called vote-a-rama, where an unlimited number of amendments could be offered by both parties. This was the third vote-a-rama this year, after Democrats prevailed through two identical exercises to push their $1.9 trillion pandemic relief package through Congress.

The marathon of nearly four dozen votes also gave Republicans a platform to hammer Democrats for trying to advance a package of this magnitude entirely without their input, as well as distinguish the process from the public works plan many of them had supported hours earlier.

“You’re spending money like drunken sailors,” declared Sen. Lindsey Graham of South Carolina, the top Republican on the Budget Committee. You’re putting in motion, I think, the demise of America as we know it. You’re putting in motion a government that nobody’s grandchild can ever afford to pay.”

The proposed changes, many of which were shot down along party lines, were nonbinding and intended more to burnish a political case against the most vulnerable Democratic senators facing reelection in 2022 than to become law. Some Republicans said the brunt of their proposals would wait until the subsequent legislation was finished, when changes could actually be adopted.

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“The next vote-a-rama is the one that really matters, because then you’re firing with live ammo,” said Sen. Pat Toomey, R-Pa. “So I’m much more interested in that one than this one.”

The hourslong stretch began with a vote that would prohibit funding or regulations to establish the Green New Deal, with Sen. John Barrasso, R-Wyo., declaring that any such provision “will reduce the quality of life for American people — millions and millions of Americans will suffer.”

“I have no problem voting for this amendment, because it has nothing to do with the Green New Deal,” Sanders shot back. The amendment passed unanimously, with the legislation’s Democratic sponsors dismissing it as “a tired and failed Republican attempt to throw speed bumps on the road to climate action.”

Democrats worked to remain in lock step to ward off many of the Republican proposals, including a provision from Sen. Chuck Grassley, R-Iowa, that would prevent changes to the cap on how much taxpayers can deduct in state and local taxes. Democrats from high-tax states, particularly New York, New Jersey and California, have made raising or repealing the cap a priority, and a partial repeal is under discussion to be included in the final legislation.

Attempts to limit the blueprint’s expected tax increases, prevent the inclusion of climate provisions or reduce its scope were often denied. Proposals to force the reopening of schools shuttered to stop the spread of the coronavirus and opposing Biden’s ban on new oil and gas leases on federal land also fell short.

But a few amendments signaled potentially substantive fights to come. For example, three Democrats — Sens. Mark Kelly of Arizona, Manchin and Sinema — supported a provision calling for electric vehicle tax credits to be means-tested. And Manchin joined Republicans in backing the Hyde Amendment, which bans federal funding for abortion and which Democrats are aiming to remove from the spending bills needed to fund the government.

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Manchin also voted with Republicans to adopt an amendment from Sen. Tom Cotton, R-Ark., to try to block the teaching of so-called critical race theory in public schools.

Around midnight, Democrats voted down, 50-49, an amendment from Sen. Mitt Romney, R-Utah, that aimed to block any new tax increases.

Democrats supported some amendments as a way to defang Republican attempts to weaponize the process, as they did with the Green New Deal amendment. Among those was an amendment put forward by Sen. Tommy Tuberville, R-Ala., to penalize local governments that reduced funding for police, reflecting a conservative push to attack Democrats over calls to defund or abolish police departments.

“I am so excited — this is perhaps the highlight of this long and painful and torturous night,” an exuberant Sen. Cory Booker, D-N.J., proclaimed in response, urging his colleagues to “not walk, but sashay down there” to vote for the amendment. “I’m sure I will see no political ads attacking anybody here over defunding the police.”

A dozen Senate committees will now begin haggling over the details of the final reconciliation package. Schumer has said he hopes to have the legislation completed by the week of Sept. 15, for the full caucus to review.