Islamic State's claim was carried by Amaq, the organization's news agency.
"The armed attack that targeted a gay night club in the city of Orlando in American state of Florida which left over 100 people dead or injured was carried out by an Islamic State fighter," said the Amaq statement.
At least 50 people were killed and 53 others were wounded in the Pulse nightclub before the suspected gunman was shot to death by police.
The suspected shooter was identified by authorities as Omar Mateen, a Florida resident who a senior FBI official said might have had leanings toward Islamic State.
The FBI official cautioned, however, that proving the suspected link to radical Islamism required further investigation.
Two US officials familiar with the investigation into the massacre said that no evidence had yet been found showing a direct link between the massacre and Islamic State or any other militant group.
The officials, who spoke on condition of anonymity, also said they had yet to see any direct contacts between any extremist group and the suspect.
Speaking at the White House, US President Barack Obama called the attack "an act of terror" and an "act of hate," and said the FBI would "spare no effort" to determine whether the suspect had been inspired by any extremist group.
The two officials familiar with the investigation said a leading theory was that the suspect somehow was inspired by Islamic militants.
One official said early information, the nature of which he did not disclose, indicated that the shooter was motivated by a mixture of "hate" and religion.
Federal authorities believe the shooter was Mateen, the US-born son of Afghan immigrants, he said.
'Act of terrorism'
US Representative Adam Schiff of California, the senior Democrat on the House Intelligence Committee, said in a statement issued after a briefing on the massacre that several factors indicated the attack was an Islamic State-inspired "act of terrorism."
He noted that the incident occurred during the Islamic holy month of Ramadan, that Islamic State had called for attacks during that period, the target was an LGBT nightclub and it was hit during Gay Pride weekend.
Moreover, he said, that if accurate, "according to local law enforcement the shooter declared his allegiance to ISIS (Islamic State)."
An audio message purportedly issued last month by the spokesman of Islamic State called on followers to launch attacks in the United States and Europe during Ramadan, which began on June 5 in the United States.
“Ramadan, the month of conquest and jihad. Get prepared, be ready ... to make it a month of calamity everywhere for the non-believers ... especially for the fighters and supporters of the caliphate in Europe and America," said the statement allegedly made by Abu Muhammad al-Adnani and distributed over Twitter accounts usually associated with Islamic State.
“The smallest action you do in their heartland is better and more enduring to us than what you would if you were with us. If one of you hoped to reach the Islamic State, we wish we were in your place to punish the Crusaders day and night,” said the audio clip, the authenticity of which could not be verified.
