The interim president of Columbia University abruptly left her post Friday evening as the school confronted the loss of hundreds of millions of dollars in federal funding and the Trump administration’s mounting skepticism about its leadership.

The move came one week after Columbia bowed to a series of demands from the federal government, which had canceled approximately $400 million in essential federal funding, and it made way for Columbia’s third leader since August. Claire Shipman, who had been the co-chair of the university’s board of trustees, was named the acting president and replaced Dr. Katrina Armstrong.

The university, which was deeply shaken by a protest encampment last spring and a volley of accusations that it had become a safe haven for antisemitism, announced the leadership change in an email to the campus Friday night. The letter thanked Dr. Armstrong for her efforts during “a time of great uncertainty for the university” and said that Ms. Shipman has “a clear understanding of the serious challenges facing our community.”

Less than a week ago, the Trump administration had signaled that it was satisfied with Dr. Armstrong and the steps she was taking to restore the funding. But in a statement on Friday, its Joint Task Force to Combat Antisemitism said that Dr. Armstrong’s departure from the presidency was “an important step toward advancing negotiations” between the government and the university.

The statement included a cryptic mention of a “concerning revelation” this week, which appeared to refer to comments from Dr. Armstrong at a faculty meeting last weekend. According to a faculty member who attended, Dr. Armstrong and her provost, Angela Olinto, confused some people when they seemed to downplay the effects of the university’s agreement with the government. A transcript of the meeting had been leaked to the news media, as well as to the Trump administration, according to two people familiar with the situation.

Ms. Shipman, a journalist with two degrees from Columbia, is taking charge of one of the nation’s pre-eminent universities at an extraordinarily charged moment in American higher education.

The federal government is threatening to end the flow of billions of dollars to universities across the country, many of which are facing inquiries from agencies that range from the Justice Department to the Department of Health and Human Services.

But the Trump administration’s punitive approach to universities is playing out most acutely at Columbia. The university, a hub of last spring’s campus protest movement against the war in Gaza, has spent months confronting accusations from one side that it condoned antisemitic behavior and permitted lawlessness to dominate, and from the other that it stifled academic and political speech.

The government’s move this month to cut off hundreds of millions of dollars in support to Columbia — which draws roughly a fifth of its operating revenues from Washington — represented a dire threat to the university. The government told Columbia it would consider restarting those grants and contracts only after the university agreed to a list of demands.

Last week, it fell to Dr. Armstrong to announce that Columbia had done so.

Among other steps, Columbia said it would have 36 campus safety officers with arrest powers, a shift with enormous resonance at a university that has a long history of campus activism and fraught ties with law enforcement. The university also said it would adopt a formal definition of antisemitism, review its admissions policies and, in a turn that was especially alarming to professors who cherish academic freedom, impose new oversight of the university’s Middle Eastern, South Asian and African Studies Department.

Although university officials said they had already been considering some of the government’s demands, Columbia’s acquiescence drew significant condemnation on the campus and beyond. Other higher education leaders watched nervously, fearing that the university’s decision, without mounting a court challenge that many felt stood a reasonable chance of success, would provoke the government to target other universities.

Two days before Columbia announced its decision, the government said it would withhold about $175 million in funding to the University of Pennsylvania because the school allowed a transgender woman to be a member of its women’s swim team in 2022.

Dr. Armstrong’s departure from the presidency was about as abrupt as her ascension to it last summer. Then, not long before classes began, Nemat Shafik resigned as president, ending a 13-month tenure that had led to global criticism of Columbia.

“Dr. Armstrong accepted the role of interim president at a time of great uncertainty for the university and worked tirelessly to promote the interests of our community,” David J. Greenwald, the chair of the board of trustees, said in a statement on Friday. The university said that Dr. Armstrong would remain at Columbia as the head of the university’s medical center.

In an email addressed to colleagues on Friday evening, Dr. Armstrong said it had been “a singular honor to lead Columbia University in this important and challenging time.”

“My heart is with science, and my passion is with healing,” she added. “That is where I can best serve this University and our community moving forward.”

The Wall Street Journal first reported that Dr. Armstrong would be leaving the Columbia presidency.

Less than a week ago, Linda McMahon, the Trump administration’s education secretary, had suggested that she was pleased with Dr. Armstrong’s work.

“She knew that this was her responsibility to make sure that children on her campus were safe,” Ms. McMahon, told CNN last weekend. “She wanted to make sure there was no discrimination of any kind. She wanted to address any systemic issues that were identified relative to the antisemitism on campus. And they have worked very hard in a very short period of time.”

Ms. McMahon said then that Columbia was “on the right track so that we can move forward,” but she stopped short of saying that the government would revive its varied funding agreements with Columbia.

But the government’s concern about Dr. Armstrong’s commitment was clear by Tuesday, prompting her to release a public letter reaffirming her seriousness.

“Any suggestion that these measures are illusory, or lack my personal support, is unequivocally false,” she wrote to Columbia’s community.

Brent R. Stockwell, the chair of Columbia’s department of biological sciences, said that despite the criticism this week from some quarters, Dr. Armstrong had maintained the backing of those who felt that reclaiming the university’s federal funding was paramount.

“She had quite a lot of support,” Professor Stockwell said.

He said he could not speak for everyone but that many in the school’s research community “aren’t willing to give up on the dream that Columbia can better the world and the lives of Americans through research. That is what we are trying to achieve, and that requires federal funds.”

Representative Tim Walberg, Republican of Michigan, and the chairman of the House Committee on Education and the Workforce, which has been seeking student discipline records from Columbia, said the school must redouble its efforts to overcome its failure “to uphold its commitment to Jewish students and faculty.”

Representative Walberg also signaled to the new interim president that she would not receive a honeymoon. “Ms. Shipman, while we wish you all good success, we will be watching closely,” Representative Walberg said.

Adarsh Pachori, an engineering graduate student at Columbia, said he was left “uncomfortable and worried” by the sudden change in university leadership.

“This resignation along with the funding withdrawal, talk of deportations and government involvement in general is frustrating,” said Mr. Pachori, who was walking on campus Friday night. “It is starting to seem that Columbia administration simply caves to the demands of the U.S. government instead of upholding the beliefs and values that are promised at Columbia.”

Anvee Bhutani contributed reporting.