WASHINGTON — Senator Joe Manchin III announced on Friday that he would oppose the nomination of Neera Tanden, President Biden’s pick to lead the Office of Management and Budget, imperiling her prospects for confirmation in an evenly divided Senate.

The announcement by Mr. Manchin, Democrat of West Virginia, underscored the fragility of the ambitions of the new Democratic majority in the Senate and the outsize power that any one senator holds over the success of Mr. Biden’s administration and agenda.

The fate of the nomination is now in the hands of a party that Ms. Tanden has frequently criticized in the past, particularly moderate Republicans she has previously scorned. Ms. Tanden would need the support of at least one Republican senator in order to to be confirmed, with the vote of Vice President Kamala Harris needed to break a tie.

Given Ms. Tanden’s previous litany of critical public statements and posts on Twitter against members of both parties, it is unclear whether such support exists.

Mr. Manchin cited statements from Ms. Tanden that were personally directed at Senators Mitch McConnell of Kentucky, the Republican leader; Bernie Sanders, the Vermont independent now in charge of the Senate Budget Committee; and other colleagues.

“I believe her overtly partisan statements will have a toxic and detrimental impact on the important working relationship between members of Congress and the next director of the Office of Management and Budget,” said Mr. Manchin, who will also cast a decisive vote on Mr. Biden’s $1.9 trillion stimulus plan. “For this reason, I cannot support her nomination. As I have said before, we must take meaningful steps to end the political division and dysfunction that pervades our politics.”

Mr. Biden told reporters on Friday that he did not plan to withdraw her nomination.

“I think we are going to find the votes and get her confirmed,” he said.

Jen Psaki, the White House press secretary, reiterated that position in a statement: “Neera Tanden is an accomplished policy expert who would be an excellent budget director and we look forward to the committee votes next week and to continuing to work toward her confirmation through engagement with both parties.”

But the lack of support from Mr. Manchin could be enough to derail the nomination altogether, should Republicans remain united against her selection.

Ms. Tanden would be the first woman of color to head the Office of Management and Budget, an agency that is critical to the execution of the administration’s economic and policy agendas. But Mr. Biden’s decision to nominate her even before Democrats won control of the Senate in January stunned several lawmakers and aides on Capitol Hill, given the slim margins in the upper chamber and Ms. Tanden’s prolific venom on social media.

A senior adviser to Hillary Clinton’s 2016 presidential campaign, Ms. Tanden had frequently clashed with Mr. Sanders and other prominent liberals long after the conclusion of the primary race that year. Once she was formally nominated to oversee the budget agency, Ms. Tanden deleted more than 1,000 negative tweets, and liberal senators rallied to her defense.

But she faced tough questioning from both Republicans and Democrats during her two confirmation hearings this month, with lawmakers from both parties examining her previous tweets and statements and grilling her over the millions of dollars of corporate donations that her think tank, Center for American Progress, received.

Republicans spent the first hour of her first hearing before a Senate homeland security committee asking Ms. Tanden to explain her past tweets and why she deleted more than 1,000 shortly after the November election.

Senator Rob Portman, Republican of Ohio and a former director of the Office of Management and Budget, read aloud posts in which she called Mr. McConnell “Moscow Mitch” and said that “vampires have more heart than Ted Cruz,” a Republican senator from Texas.

Her second hearing was no less fiery, with Mr. Sanders confronting Ms. Tanden over her history of leveling personal attacks on social media. He also demanded details about the donations the Center for American Progress received from corporations under her leadership and a promise that it would not influence her work in the Biden administration.

Ms. Tanden apologized to lawmakers during both hearings, saying she regretted many of her previous remarks, and she vowed that the donations would carry no weight over her role as budget director.

“I worry less about what Mrs. Tanden did in the past than what she’s going to do in the future,” Mr. Sanders said Friday night on CNN. “I’m talking to her early next week.”

Many Democrats accused Republicans of unfairly singling out Ms. Tanden’s social media posts after years of evading queries about President Donald J. Trump’s tweets, even when they espoused racist and offensive commentary or targeted their own colleagues.

“Honestly, the hypocrisy is astounding,” Senator Chuck Schumer of New York, the Democratic leader, said at the time. “If Republicans are concerned about criticism on Twitter, their complaints are better directed at President Trump. I fully expect to see some crocodile tears spilled on the other side of the aisle over the president-elect’s cabinet nominees.”

Mr. Biden’s pick for deputy director of the agency, Shalanda Young, is respected by lawmakers and aides in both parties after serving as staff director for House Democrats on the Appropriations Committee. The first Black woman to serve in the role, she helped wrangle the compromise that ended the nation’s longest government shutdown in 2019 and the coronavirus relief packages Congress approved in 2020.

Jim Tankersley and Alan Rappeport contributed reporting.