On Wednesday night, Ron Klain, the White House chief of staff, went on television to proclaim that the Biden administration was still “fighting our guts out” to get Neera Tanden confirmed as the head of the Office of Management and Budget.

It was a fight that Mr. Klain and others in the West Wing had not expected to have to wage.

After Democrats picked up two Senate seats in twin Georgia runoff elections in January, giving the party control of the Senate and the incoming Biden team more leeway in its nominations, Ms. Tanden was seen as a strong pick to serve as budget director. Mr. Klain pushed hard for Ms. Tanden, a longtime friend, even while some other aides worried picking her would create a distraction and require the White House to expend political capital best used to pass the relief bill.

But the back-of-the-envelope math looked good for her confirmation, even accounting for the concerns about her being seen as partisan and unstrategically belligerent in social media posts.

The White House did not have promised Republican votes, but officials were hearing encouraging rumblings. Senator Mitt Romney of Utah, for instance, had told mutual contacts he was inclined to give the president his pick, according to two people involved in the process.

Democrats close to the administration said Ms. Tanden had been expecting a level of Republican support similar to Alejandro Mayorkas, the homeland security secretary, who was confirmed with six Republicans joining 50 Democrats to vote for his confirmation.

But by Thursday afternoon, the fight to confirm Ms. Tanden had come down to whether Mr. Biden’s team could scrounge up one lonely Republican to support her nomination. (With Senator Joe Manchin III, Democrat of West Virginia, in the “no” column, at least one Republican would be needed to join all Democrats in support.)

After Senator Charles E. Grassley, Republican of Iowa, said he would not vote to confirm Ms. Tanden, there was only one option left on the table: Senator Lisa Murkowski, Republican of Alaska. Even Mr. Romney, who had been in the White House’s unofficial “likely” column, said he could not support a nominee “who has issued a thousand mean tweets.”

Murkowski could still vote to confirm Ms. Tanden. But even if she does, this is not how the Biden team expected the process to play out.

Of the Republicans who had generally been helpful and not totally oppositional to the Biden administration, only Senator Susan Collins of Maine was a locked-in “no” vote for Ms. Tanden, according to one official involved in the process.

With no overarching concerns over Ms. Tanden’s nomination, the White House focused its time and energy instead on preparing two appointees it had assessed to be its most vulnerable cabinet members: Representative Deb Haaland, who Mr. Biden nominated to serve as interior secretary; and Xavier Becerra, nominated to serve as secretary of health and human services.

White House officials said the dam seemed to break for Ms. Tanden after Mr. Manchin said he would not support her nomination. Republican opposition jumped after his vote, and some officials viewed those “no” votes as an opportunistic pile-on.

Biden allies involved in the process said Mr. Klain knew Ms. Tanden’s nomination would be somewhat contentious.

But he and others did not expect her tweets to make her more contentious than other potential nominees. Progressives like Representatives Alexandria Ocasio-Cortez and Ilhan Omar, for example, were staging protests over the possibility of Bruce Reed, Mr. Biden’s former chief of staff, leading the budget department before the nomination went to Ms. Tanden. White House officials assumed nominees for other posts would face more opposition from Republicans.

White House officials conceded that Mr. Klain miscalculated the opposition to Ms. Tanden. But they also put the struggle over her nomination in context, noting that former President Barack Obama had 57 Democratic Senators and still lost three cabinet picks in his first year. The Biden administration, in contrast, has pushed through a historically diverse and progressive cabinet with less reliable Democratic support in the Senate.

On Thursday, Jen Psaki, the White House press secretary, told reporters that “The president nominated Neera Tanden because she is qualified, because she is experienced, because she has a record of working with people who agree and disagree with her.”

“We’re continuing to fight for her confirmation,” she said.

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