The agency’s handling of Weber revealed broader dysfunction at the U.S. agency that provides health care to 2.6 million Native Americans, often in some of the nation’s poorest and most remote communities. The Journal and Frontline later reported that the agency had hired dozens of doctors with track records of malpractice, licensure sanctions and even criminal convictions who went on to harm patients at IHS hospitals.

Weber was convicted in South Dakota in September of abusing four of his patients at the IHS’s Pine Ridge hospital and his government housing unit there. One victim testified at the trial that Weber had used narcotics to subdue him before sexually assaulting him, and another described escalating assaults during a series of visits in hospital exam rooms.

In delivering the sentence, Chief U.S. District Judge Jeffrey Viken described his four-decade legal career before pronouncing he had never seen anything like the “abuse of trust you have inflicted on these men.” Judge Viken imposed 45 years and an $800,000 fine in addition to the five life sentences.

Three of the victims he was convicted of abusing were present in the crowded courtroom and spoke of the impact of Weber’s crimes. “I need help, I try to get help,” said one of the victims. “But I refuse to go to the IHS.”

In 2018, Weber was convicted in a separate trial in Montana for abusing two former patients there, and sentenced to more than 18 years in prison. He appealed that conviction, but a higher court affirmed it Monday, hours before his South Dakota sentencing.

An IHS manager in Montana concluded in 1995 that Weber might be molesting his patients, and ordered his supervisor to fire him. But, just weeks later, Weber re-emerged with another agency job, at Pine Ridge. There, he survived multiple investigations and years of complaints by colleagues about the parade of boys who visited his home at night.

After hearing his sentence Monday, Weber had no visible reaction. His lawyer, Harvey Steinberg, declined to comment as he left the courtroom.

U.S. Attorney Ron Parsons said the case had focused the federal government’s attention on accountability for such abuses. “This has been a wake-up call for everyone, including us,” he said.

Rear Adm. Michael Weahkee, the director of the IHS, said in a statement, “The actions of this individual were reprehensible, and we sincerely regret the harm caused to the children involved.”

The investigation that led to the convictions began after a prosecutor at the Oglala Sioux Tribe, which is based at Pine Ridge, began looking into the case in 2015. The prosecutor, Elaine Yellow Horse, learned the name of one boy who had earlier told associates that Weber had abused him.

Ms. Yellow Horse, now a law student, attended the sentencing hearing Monday in Rapid City, at times looking down and wringing her hands as victims described the damage Weber had inflicted. She said, “I hope they can restart their lives now that they have had their voices heard.”

The tribe, which doesn’t have jurisdiction over non-Native American offenders, passed the lead on to investigators at the Bureau of Indian Affairs, which in turn enlisted the Department of Health and Human Services’ Office of the Inspector General. Those federal agents then identified a series of other victims spanning the two states.

The Oglala Sioux Tribe’s current president, Julian Bear Runner, addressed the court, saying Weber had told him when he was a teenager that he didn’t need to bring an adult for a return visit.

Reports by the Journal and Frontline about Weber have prompted at least five federal investigations. One of them, an independent review commissioned by the IHS, recently ended. A private contractor hired by the IHS reviewed three decades of agency records concerning Weber and interviewed about 50 people involved in the case, people familiar with the findings show.

But the agency has declined to disclose the report, arguing it is a confidential quality-assurance record that is not public by law. IHS told congressional offices it plans to eventually release a summary of “broad findings and recommendations.”

Mark Butterbrodt, a former IHS pediatrician who repeatedly accused Weber of sexual misconduct, said he was interviewed by investigators in that probe. He said they showed him records indicating an IHS official had signed off on renewing Weber’s patient-care privileges at Pine Ridge just one day after the disgraced doctor had submitted a form alerting the agency he was under investigation by the South Dakota board of medicine.

Dr. Butterbrodt, speaking at the hearing Monday, described his efforts over about 15 years to call attention to Weber’s conduct. “Not one physician stood with me on that medical staff,” he said. Instead, he said, they snickered about their colleague’s behavior.

A top medical official at the hospital at the time said her colleagues investigated allegations against Mr. Weber but found no hard evidence of misconduct.

At the height of the courtroom drama that unfolded Monday, the first victim, who now is incarcerated, shook his head and remained seated in shackles when a prosecutor asked if he wished to speak.

Then, two of his childhood friends—also victims of Weber—spoke to the court about their experiences. One turned to the shackled man who’d kept his silence and said, “I love you.”

The prisoner changed his mind. In a strained speech, he told the court he had lost his ability to trust anyone as a result of Weber’s abuse: “I look at each and every one of you as potential predators.”

And he turned to his friends seated in the audience and told them, “You gotta stay strong.”

Write to Christopher Weaver at christopher.weaver@wsj.com