Otto Warmbier was pronounced dead on Monday at 2:20 p.m local time, in his home state of Ohio, according to a statement from his family members.
He was 22-years old.
The University of Virginia student was returned to his family in the U.S. last week, but he was already in a comatose state, suffering from a "serious neurological injury".
His doctors said last week that Mr. Warmbier had lost a significant amount of brain tissue, and was unresponsive to his surroundings despite being awake.
Mr. Warmbier's family said he was surrounded by his loved ones at the time of his passing, and that he had "completed his journey home".
While thanking the medical staff for their efforts, they said Mr. Warmbier's death was inevitable, given the "awful, torturous mistreatment" he suffered in North Korea.
In his immediate reaction to the news, President Trump called North Korea a brutal regime that does not respect the rule of law or basic human decency.
He also released a written statement offering condolences to Mr. Warmbier's family and vowing to prevent similar tragedies from befalling innocent people in the future.
Otto Warmbier was arrested on charges of subversion by North Korea last year, while he was touring the country, for allegedly trying to steal a propaganda banner from his hotel room.
His final public appearance came last March in a show trial, where following a tearful courtroom confession, he was handed a 15-year jail sentence with hard labor.
Three U.S. citizens remain in North Korea after being detained by the regime.
Washington has accused Pyongyang of using American detainees as political bargaining chips, while the North claims they are spies sent to overthrow the regime.
Yu Joonhee, Arirang News.