The claims were made in newly released summaries of interviews conducted by the FBI with detainees at the military-run prison in 2002 and 2003.
The declassified papers revealed the treatment of the Koran was a key point of contention between the prisoners and their guards, one that prompted hunger strikes and threats of mass suicide.
The most common complaint dealt with the handling of the Koran by guards or its being taken away from detainees as a form of punishment.
In some cases, the detainees admitted to not having witnessed the alleged mistreatment themselves.
But detainees also alleged the Koran had been thrown or kicked by guards, and one said it had been flushed in a toilet, according to the documents.
In a summary dated August 1, 2002, a detainee told his FBI interviewer the guards “flushed a Koran in the toilet. The guards dance around when the detainees are trying to pray. The guards still do these things.”
In another interview, a prisoner said an uprising at the prison in July 2002 started when a detainee claimed a guard had dropped a Koran.
“In actuality, the detainee dropped the Koran and then blamed the guard. Many other detainees reacted to this claim, and this initiated the uprising,” the summary said.
Names and other details were blacked out in the documents, which were released in response to a lawsuit by the American Civil Liberties Union.
The interview summaries contain a litany of other allegations by detainees.
They included claims they were beaten by guards, sexually molested by female interrogators, shown pornographic images or had their heads and beards shaved as punishment.
The ACLU said the documents showed the Pentagon was aware of such allegations being made at Guantanamo Bay long ago, but had repeatedly turned a blind eye to “mounting evidence of widespread abuse”.
The disclosure echoes a similar claim made in Newsweek magazine earlier this month, which it was later forced to retract.
The Newsweek story sparked protests across the Muslim world and riots in Afghanistan that killed at least 14 people.
Last week, the Pentagon angrily denied the story, saying it had seen “no credible and specific allegations” about putting a Koran in a toilet.