The guilty plea will avert a federal trial in the closely watched case over the killing of UnitedHealthcare CEO Brian Thompson, a brazen crime that was condemned by public officials but became emblematic of popular frustration with health insurance industry practices.
It could also allow him to seek dismissal of state murder charges and delay an upcoming trial in that case.
US District Judge Margaret Garnett told Mangione that if he pleaded guilty he could face a maximum sentence of life in prison on each count.
Garnett set Mangione's sentencing for December 18.
Mangione's lawyer Karen Friedman Agnifilo said there was no plea agreement with prosecutors.
Thompson led UnitedHealth Group's insurance unit before he was shot dead in the early morning of December 4, 2024, outside the hotel where an investor conference was taking place.
Thompson's widow sat in the front row of the gallery with other members of his family.
Mangione, 28, said in court that he researched details of UnitedHealthcare's annual investor conference in December 2024 after suffering a broken back and navigating the health insurance system.
He said he then used a 3-D printer to make part of a gun and travelled to New York with the intent of killing Thompson.
"I shot Mr Thompson in Manhattan and he died," Mangione said.
Graphic footage of the killing and a five-day manhunt for a suspect made the case a media fixture and social media sensation.
Mangione was arrested in Pennsylvania.
He had previously pleaded not guilty in April 2025 to murder, weapons and stalking charges brought by Manhattan federal prosecutors.
Garnett threw out the murder and weapons charges over legal technicalities in a surprise ruling in January 2026.
The decision eliminated the possibility that Mangione would face the death penalty in the federal case although he still faces a possible sentence of life without parole if convicted on the remaining stalking charges.
His federal trial was most recently set for January.
Mangione separately pleaded not guilty in December 2024 to state terrorism, murder, weapons and forgery charges brought by Manhattan District Attorney Alvin Bragg.
The terrorism charges were thrown out by a judge in September 2025.
A trial in that case is scheduled for September 8 before Justice Gregory Carro in Manhattan.
Mangione would face 25 years to life in prison if convicted of second-degree murder.
The guilty plea in the federal case could allow Mangione to seek dismissal of the murder charge under New York's double jeopardy law, which protects people from being prosecuted twice for the same conduct.
Bragg's office would oppose the move, arguing that the murder charge is legally distinct from the federal charges.
Whoever loses would likely seek an emergency appeal.
