The attacker swore allegiance to IS in a 911 call around the time of the attack
Islamic State has claimed responsibility for the Orlando nightclub shooting, which killed 50 people and injured 53 others, according to the Amaq news agency, which is tied to the group.
"The armed attack that targeted a gay nightclub in the city of Orlando in the American state of Florida which left over 100 people dead or injured was carried out by an Islamic State fighter," Amaq said.
The attack is the deadliest mass shooting in US history, eclipsing the 2007 Virginia Tech massacre which left 32 people dead.
The Islamic State claim comes after US media reported that a man, suspected to have been the gunman, swore allegiance to IS in a 911 call around the time of the attack.
He also reportedly mentioned the 2013 Boston Marathon bombings, according to CNN.
A number of officials have cautioned, however, that possible links between the gunman and Islamic State further investigation.
The gunman, who is among the dead, has been named as 29-year-old Omar Mateen of Port St. Lucie Florida, a US citizen of Afghan descent.
Armed with a device thought to be a bomb, an assault rifle and a handgun, Mateen opened fire in the busy club Pulse in the early hours of Sunday morning before taking hostages.
Orlando Police have said that the Pulse nightclub gunman legally purchased the firearms in Florida within the last week.
He was involved in a three-hour stand-off with officers before SWAT teams stormed the building and shot him dead.
US President Barack Obama has condemned the massacre as an "act of terror and an act of hate".
Confirming that the number of dead had risen from 20 to 50, Orlando Mayor Buddy Dyer told a press briefing: "Today we're dealing with something that we never imagined and is unimaginable.
"There's blood everywhere".
He said a state of emergency has been declared in the city of Orlando and that he had asked Florida's governor to issue a state-wide state of emergency due to the "scale of the crime".
In a statement, House Homeland Security Chairman Michael McCaul said: "This appears to be the worst terrorist attack on American soil since 9/11, and it is a sobering reminder that radical Islamists are targeting our country and our way of life."
However, US Congressman Alan Grayson told reporters there is currently no "direct information" to suggest the gunman was associated with any particular group.
He told the media that authorities are investigating whether the attack was a "hate crime perpetrated against gays."
The gunman's father has also told US media the attack may have been triggered by the sight of a gay couple kissing in Miami, adding that it had "nothing to do with religion".
"He saw two men kissing each other in front of his wife and kid and he got very angry," Mir Seddique told NBC News.
The attack unfolded just after 2am when an officer working as a security guard at the club raised the alarm and engaged in a gunbattle with Mateen. The gunman then took a number of hostages inside the popular gay club.