Maxwell was on Thursday charged with sex trafficking underaged girls to be sexually assaulted by the late disgraced financier between 1994 and 1997.
The British socialite, 58, was arrested by the FBI and indicted on several charges, including enticing a minor to travel to engage in illegal sex acts.
Speaking at a press conference, FBI New York assistant director William Sweeney said: “Today we announce the arrest of one of the villains in this investigation.”
Maxwell has for years been accused by many women of recruiting them to give Epstein massages, during which they were pressured into sex – accusations which she has strongly denied.
Epstein, 66, killed himself in a federal detention centre in New York last summer while awaiting trial on sex trafficking charges.
Mr Sweeny told reporters that investigators had been “discreetly keeping tabs on Maxwell’s whereabouts”.
He continued: “More recently we learned she had slithered away to a gorgeous property in New Hampshire, continuing to live a life of privilege while her victims live with the trauma inflicted upon them years ago.
“We alleged that from at least 1994 through at least 1997 Ms Maxwell assisted Jeffrey Epstein’s abuse of minor girls by helping to recruit, entice, groom and abuse children under 18.”
Maxwell was arrested in Bradford, New Hampshire that morning and remains in police custody. She is due to appear in court later on Thursday.
Audrey Strauss, acting US attorney for the southern district of New York, said Maxwell had played a “critical role” in helping Jeffrey Epstein “identify, befriend and groom minor victims for abuse”.
“Today, after many years, Ghislane Maxwell finally stands charged for her role in these crimes,” she said.
Setting out the charges against the defendant, Ms Strauss said: “Maxwell was among Epstein’s closest associates and helped him exploit girls who were as young as 14-years-old.
“Maxwell played a critical role in helping Epstein to identify, befriend and groom minor victims for abuse.
Ms Strauss said Maxwell had pretended to be a woman the victims could trust, all while she was “setting them up to be sexually abused by Epstein and in some cases by Maxwell herself”.
“These charges we have announced today are the latest result into our investigation into Epstein and the people around him who facilitated his abuse of minor victims, that investigation remains ongoing,” she explained.
The prosecutor said she and her office were doing everything “to bring justice to individuals who enabled, facilitated and participated in the acts of abuse”, adding that “combating the exploitation of children is a priority of our office.”
She urged anyone who believes they may have been abused by Maxwell and Epstein to contact the FBI.
Ms Strauss said the FBI would be “seeking detention” for Maxwell and that her team would be “in dialogue with the Bureau of Prisons about it”.
Maxwell is charged with conspiracy to entice minors to travel to engage in illegal sex acts, enticement of a minor to travel to engage in illegal sex acts and conspiracy to transport minors with intent to engage in criminal sexual activity. She was also charged with two counts of perjury.
The former socialite has repeatedly denied wrongdoing and called some of the claims against her "absolute rubbish."
Among the most sensational accusations was a claim by one Epstein victim, Virginia Roberts Giuffre, that Maxwell arranged for her to have sex with Prince Andrew at her London townhouse.
He has categorically denied her story and Maxwell said in one deposition that Giuffre was "totally lying."
The duke was not mentioned by name in the indictment, and the charges covered Maxwell's dealings with Epstein between 1994 and 1997 – a period well before his alleged encounters with Giuffre in 2001.
Ms Strauss said she would "welcome Prince Andrew coming in to talk with us," but did not answer further questions from reporters regarding accusations against him.
Brad Edwards, an lawyer who represents Giuffre and several other Epstein victims said his clients were relieved by the charges against Maxwell.
"Today is a very good day," he said.