The U.S. attorney’s office in Chicago is among the most prestigious in the country, known for winning ambitious cases against everyone from Al Capone to the former Illinois governor Rod R. Blagojevich.

But the Trump administration’s immigration sweep in Chicago last fall has left the office in crisis.

The office brought a wave of doomed cases that accused protesters and immigrants of assaulting federal officers. That accelerated an exodus of veteran prosecutors, some of whom felt they’d been wrongly pressured into pursuing the charges, former prosecutors said in interviews.

The heads of all seven sections of the Chicago office’s criminal division have left in the past year, as have many of their successors and deputies.

More than 100 former federal prosecutors from the office recently signed a letter criticizing Andrew S. Boutros, the U.S. attorney for the Northern District of Illinois, saying that “actions taken by leadership in the last year have tarnished the reputation” of the office.

Under Mr. Boutros, the office brought dozens of federal assault charges against immigrants and U.S. citizens who protested the Chicago sweep, known as Operation Midway Blitz. To handle the flood of cases, Mr. Boutros redeployed prosectors from across the criminal division. He also eliminated the stand-alone national security section — long considered a leader in terrorism cases — and shifted the work to an unrelated unit.

The New York Times identified assault cases against 62 people that Mr. Boutros’s office brought under the once-obscure federal statute 18 U.S.C. 111. They have flopped at an extraordinary rate. Some 59 charges were abandoned by prosecutors or dismissed by judges, an analysis by The Times found. Only one resulted in a guilty plea, and there have been no convictions in court. Two cases are pending.

That 2 percent success rate is a stark reversal for the Justice Department, which wins an average of more than 90 percent of criminal cases.

The failed charges in the Chicago office represent more than a quarter of the 213 such cases nationwide that federal prosecutors have abandoned or lost since the start of President Trump’s crackdown on illegal immigration last year.

Wyn Hornbuckle, a Justice Department spokesman, defended the department’s handling of assault cases and said it would protect federal officers “to the fullest extent of the law.” But he also said that prosecutors had to inform the court if “mitigating factors” were found.

Gregory Bovino, the former senior Border Patrol official who led Midway Blitz, rejected any criticism of the assault cases. He said in an interview that Mr. Boutros wasn’t nearly aggressive enough in bringing them, calling him “as weak as a limp dishrag.”

As the pursuit of flimsy cases drained morale in Chicago, more and more prosecutors, including senior leaders, resigned in dismay, former prosecutors said.

One of the office’s highest-profile recent cases involved the so-called Broadview Six, who were protesting outside the Broadview immigrant detention center last fall when they were arrested and accused of interfering with a federal agent.

After the office failed twice to persuade a federal grand jury to indict the protesters, Mr. Boutros took an unusual step. Addressing a grand jury before it discussed specific cases, he told its members that anyone “who is struggling” with immigration prosecutions should “raise your hand and identify yourself,” despite Justice Department rules against pressuring grand jurors, according to a report issued by Mr. Boutros’s office. Later that day, the grand jury handed down the indictment against the protesters.

Judge April M. Perry admonished Mr. Boutros for his office’s overall handling of the case. “Your sole goal is to do justice,” she told Mr. Boutros in May. She added, “That trust has been broken.”

Mr. Boutros apologized and moved to dismiss the case.

This month, another judge criticized Mr. Boutros, this time for giving a news conference about a sealed criminal case.

Illinois’s two senators, both Democrats, have called on Mr. Boutros to resign. But Todd Blanche, the acting attorney general, recently praised him, saying he “has steadfastly advanced President Trump’s mission to make Chicago and Northern Illinois safe for the American people.”

In a social media post in June, Mr. Boutros attributed the turmoil in his office to factors including early retirements, a hiring freeze and mismanagement under the Biden administration. He said that he is “righting the ship through significant changes and reforms to policies, procedures and practices.”

The 93 U.S. attorneys’ offices nationwide are responsible for prosecuting all manner of federal criminal cases. Mr. Boutros’s Chicago outpost is hardly the only one that has been roiled by the immigration crackdown.

In Minneapolis, for example, a half-dozen prosecutors quit in a single day in January when senior officials at the Justice Department pushed the U.S. attorney’s office to investigate the widow of Renee Good, who had been killed by an ICE agent.

But the trouble in Chicago is especially notable because of the office’s storied history.

Its lawyers have prosecuted some of the country’s biggest terrorism and corruption cases, as well as those aimed at thwarting Chinese spying, Iranian smuggling and a Russian bot farm. Barry Jonas, a longtime prosecutor in the office’s now-defunct national security section who departed last year, said he and his colleagues did “a lot of work that never saw the light of day, and a lot of it went to help keep this country safe.”

Mr. Boutros, in a statement, stressed that national security remained “one of our very top priorities” and said that folding the unit into a larger section had “been a game-changer in our response and handling of national security matters.”

Even before Midway Blitz, staffing levels were sagging. Last August, Mr. Boutros sent a note to retirees asking if any wanted to come back. Veterans of the office were astonished. “It used to be that you had to walk through the eye of a needle to get a job at the U.S. attorney’s office in Chicago,” said Ronald S. Safer, who ran the office’s criminal division in the 1990s.

Midway Blitz, which began last September, only worsened morale. Many prosecutors viewed it as “a political and largely unlawful stunt,” said Mr. Safer, who has kept in touch with former colleagues. “That’s discouraging when you join the office to do the right thing.”

Federal prosecutors in Chicago declined to bring assault charges sought by immigration officers for at least 20 people arrested during Midway Blitz, court records show. That enraged Mr. Bovino.

“Boutros would allow the perps, these folks that assaulted federal agents, to walk, and say, ‘Hey, we’ll charge them later,’” Mr. Bovino said. He added that he and Mr. Boutros had “some very spirited discussions.”

In many cases that the Chicago office did pursue, the basis for the assault allegation was thin. For example, when a Border Patrol agent confronted a Latino man who was walking down the street with his earbuds in, the agent issued a citation noting his rationale: Another person had just been apprehended on that block. The Latino man, a U.S. citizen, said he didn’t have identification on him and then brushed past an agent in body armor, who tackled him. His case was eventually dismissed.

So were more than 30 cases in which protesters received misdemeanor assault charges in the form of a ticket — something historically reserved for such offenses as trespassing.

Prosecutors said in interviews that their colleagues at times were crying in their offices, distraught about the cases they were being pressured to pursue. In the wake of the 64-day Midway Blitz, inboxes were cluttered with invitations to going-away parties at the Half Sour bar on Clark Street and the Elephant & Castle on West Adams. Three section chiefs departed in late winter.

More would follow. In May, it was back to the Half Sour to say goodbye to the head of the health care fraud section.

“Hope to see you there!” the invitation said.

Reporting was contributed by Alexandra Berzon, Will Houp, Lauren McCarthy, Mike McIntire and Jazmine Ulloa.