Warmbier, 22, who was arrested in North Korea while visiting as a tourist, had been described by doctors who examined him last week as having suffered extensive brain damage that left him in a state of "unresponsive wakefulness".
Warmbier's relatives announced his death on Monday in a statement released by UC Health Systems, saying, "It is our sad duty to report that our son, Otto Warmbier, has completed his journey home. Surrounded by his loving family, Otto died today at 2:20pm".
The family thanked the University of Cincinnati Medical Center for treating him, but said, "Unfortunately, the awful torturous mistreatment our son received at the hands of the North Koreans ensured that no other outcome was possible beyond the sad one we experienced today."
They said they were choosing to focus on the time they were given with their "warm, engaging, brilliant" son instead of focusing on what they had lost.
US President Donald Trump offered condolences to the Warmbier family and denounced North Korea as a "brutal regime" with no respect for "basic human decency".
Warmbier, a University of Virginia student, was sentenced to 15 years in prison with hard labour in North Korea, convicted of subversion after he tearfully confessed he had tried to steal a propaganda banner.
Doctors said he returned with severe brain damage, but it was not clear what caused it.
Parents Fred and Cindy Warmbier told The Associated Press news agency in a statement the day of his release that they wanted "the world to know how we and our son have been brutalised and terrorised by the pariah regime " and expressed relief he had been returned to "finally be with people who love him".
Ohio's US senators sharply criticised North Korea soon after his release.
Republican Senator Rob Portman of the Cincinnati area said North Korea should be "universally condemned for its abhorrent behaviour".
Democratic Senator Sherrod Brown of Cleveland said the country's "despicable actions ... must be condemned".
Three Americans remain held in North Korea.
Washington accuses Pyongyang of using such detainees as political pawns. Yet, North Korea alleges that the US and South Korea are sending spies to overthrow its government.
Al Jazeera's Mike Hanna, reporting from Washington, DC, said that Warmbier's death could increase pressure on US authorities to prohibit Americans from visiting North Korea.
"At present, the State Department does not forbid US citizens from travelling to North Korea - there's a strong advisory against it, but, legally, citizens are able to go there," he said.
"However, questions are now going to be asked of the State Department whether it's not time - given this most recent death and the fact that a number of other Americans are being held as detainees in North Korea - that it needs to consider imposing a formal ban on US travel to the region."
Source: Al Jazeera and news agencies