Johns Hopkins University, one of the country’s leading centers of scientific research, said on Thursday that it would eliminate more than 2,000 workers in the United States and abroad because of the Trump administration’s steep cuts, primarily to international aid programs.

The layoffs, the most in the university’s history, will involve 247 domestic workers for the university, which is based in Baltimore, and an affiliated center. Another 1,975 positions will be cut in 44 countries. They affect the university’s Bloomberg School of Public Health, its medical school and an affiliated nonprofit, Jhpiego.

Nearly half the school’s total revenue last year came from federally funded research, including $365 million from the U.S. Agency for International Development. In all, the university will lose $800 million in funding over several years from U.S.A.I.D., which the Trump administration is in the process of dismantling.

Johns Hopkins is one of the top university recipients of the funding that the administration is aiming to slash. And it appears to be among the most deeply affected of the major research institutions that are reeling from cuts — or the threat of cuts — to federal money that they depend on for research studies and running labs.

In a statement on Thursday calling it a “difficult day,” Johns Hopkins said it was “immensely proud” of its work on the projects, which included efforts to “care for mothers and infants, fight disease, provide clean drinking water and advance countless other critical, lifesaving efforts around the world.”

In a statement last week describing Johns Hopkins’s reliance on federal funding, Ron Daniels, the university’s president said, “We are, more than any other American university, deeply tethered to the compact between our sector and the federal government.”

Of the school’s total operating revenue in 2023, $3.8 billion, or nearly half, came federally funded research. The Trump administration has said that it wants to make the government leaner and more efficient by, among other measures, dramatically cutting financial support for the program, which promotes public health and food security in low-income countries.

In ordering cutbacks in the agency, which amount to a 90 percent reduction in its operations, President Trump said that it was run by “radical left lunatics” and that is was riddled with “tremendous fraud.”

Critics of the decision, however, have said the cuts are ushering in a new era of isolationism that could prove to be dangerous. Sunil Solomon, an epidemiologist at Johns Hopkins, said the cuts would lead to a resurgence in the spread of H.I.V., the virus that causes AIDS.

“What true great nations do is help other nations, but now, it seems, we’re America first,” Dr. Solomon said.

The administration has also sought to reduce the amount of money that the National Institutes of Health sends to university for research, cuts that have been blocked for now in the courts. If they go into effect, those cuts would reduce federal payments to Johns Hopkins by more than $100 million a year, according to an analysis of university figures.

The university, which receives about $1 billion a year in N.I.H. funding and is currently running 600 clinical trials, is one of the plaintiffs in a federal lawsuit challenging those cuts.

Separately, the Trump administration also has targeted specific schools for cuts. It slashed $400 million from Columbia’s budget last week based on accusations that it had failed to protect students and faculty from antisemitism.

Johns Hopkins and Columbia are on a list of 10 schools that the administration says are being scrutinized by an executive branch antisemitism task force. The administration has threatened to reduce federal funding for schools on the list, and others, that it views as being noncompliant with federal civil rights laws.

In addition to the more than 2,000 employees whose jobs have been eliminated, the university said that an additional 78 domestic employees and 29 international would be furloughed at reduced schedules.

The cuts at Johns Hopkins involve programs funded by U.S.A.I.D. through which American universities have worked with global partners, largely to advance public health and agricultural research. Secretary of State Marco Rubio said this week that 5,200 of the agency’s 6,200 contracts had been canceled and that the remaining programs would be operated directly by the State Department, eliminating the need for U.S.A.I.D., which is under the State Department.

Research projects that are being eliminated include international work on tuberculosis, AIDS and cervical cancer, as well as programs that directly benefit residents of Baltimore.

Dr. Solomon, the epidemiologist, runs a $50 million, six-year program to improve H.I.V. outcomes in India. He said the budget cuts in his program alone would result in layoffs of about 600 people in the United States and India. The program had led to, among other things, the diagnosis of almost 20,000 people with H.I.V. through contact tracing.

“It’s heartbreaking,” Dr. Solomon said. “Stopping funding isn’t going to kill you today, but in six months you’re going to see an impact around the world.”

Dr. Judd Walson runs the department of international health at Johns Hopkins, which oversaw a five-year, $200 million program to diagnose and control tuberculosis in 20 countries funded by U.S.A.I.D.

In Kampala, Uganda, he said, the program was the only way children were diagnosed.

“That’s just one example of how the sudden withdrawal of support is having real impacts on survival,” he said.

In addition to the loss of jobs at Johns Hopkins, he said, the loss of the programs will lead to a spike in communicable diseases worldwide.

What is essentially a shutdown of U.S.A.I.D. has had significant effects at universities around the country.

An organization called USAID StopWork, which is tracking the layoffs, said that overall, 14,000 domestic workers had lost their jobs so far, with thousands more anticipated.

Research by the Federal Reserve shows that universities serve as major economic engines in many agricultural regions, from Iowa to Florida, meaning that the impact of the administration’s cuts to science research will be felt in both red states and left-leaning communities like Baltimore.

The elimination of a $500 million agriculture project called Feed the Future, which funded agriculture labs at 19 universities in 17 states, means many of those labs must shutter.

At the University of Illinois Urbana-Champaign, 30 people have lost their jobs at a Feed the Future lab that worked on improving soybean cultivation in Africa, according to Peter D. Goldsmith, a professor of agriculture who ran that laboratory.

At Mississippi State University in Starkville, Miss., a fisheries laboratory was shut down, according to Sidney L. Salter, a university spokesman, who did not disclose the number of jobs lost.

Economic ripple effects of the funding cuts are expected to spread through the Baltimore area. Johns Hopkins, which enrolls about 30,000 students, is also one of Maryland’s largest private employers.