Terrified survivors -- who moments before were laughing and dancing with friends -- described how the gunman named by media as a US citizen of Afghan descent raked the club with bullets, prompting a police SWAT team to storm the venue.
"We have cleared the building, and it is with great sadness that I share we have not 20, but 50 casualties in addition to the shooter," Mayor Buddy Dyer told a mid-morning news briefing in Orlando, more than doubling the previously given death toll.
President Barack Obama was being kept up to date by his homeland security and counterterrorism aide on what Florida officials are investigating as a terrorist attack.
FBI official Ronald Hopper told reporters officials were "confident" there was no immediate further threat to the area, or to the US.
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Because of the scale of the crime, however, Orlando's mayor declared a city-wide state of emergency and has asked the Florida governor to take the same measure state-wide. The federal government has offered its full support with the probe.
Police have yet to officially identify the gunman but US TV networks quoting law enforcement sources named him as Omar Mateen, who was born to Afghan parents in 1986 and lives in Port St Lucie, Florida, about two hours drive from Orlando.
Hopper said authorities were looking into whether the suspect had "leanings" toward Islamic extremism, but Florida officials also invited a local Islamic leader to address the media in a bid to preempt a possible backlash against the Muslim community.
The chaotic events unfolded over a three hour period, beginning at around 2 am (0600 GMT) when shots rang out amid the throbbing music at the Pulse Orlando nightclub near closing time.
Police said the shots were fired by a gunman armed with an assault rifle and a handgun.
"The suspect at some point went back inside the club where more shots were fired. This did turn into a hostage situation," he told reporters.
"At approximately 0500 hours (0900 GMT) this morning, the decision was made to rescue hostages that were in there."
It was unclear whether all the victims were killed by the
gunman or if some died in the ensuing shootout with police.
The attack coincides with gay pride month in the United States, with festive marches and events being held all over the country including in Orlando last week.
Mina said there was no indication of a link between the two shootings.
Speaking to Sky News, clubber Ricardo Negron, who was inside when the shooting began, described how the gunman raked the club with bullets.
"People just dropped on the floor. I guess the shooter was shooting at the ceiling because you could see all the glass from the lamps falling," he told the network.
"There was a brief pause in the shooting and some of us just got up and ran out the back."
The Pulse club advertises itself online as "Orlando's hottest gay bar." On its Facebook page, the club warned patrons: "Everyone get out Pulse and keep running."
Witness Christopher Hanson said he heard "loud banging noises, like gunshots going off."
"I didn't see any of the actual shooters. I just saw bodies going down and I was ordering a drink at the bar.
He said there was "blood everywhere."
Rosie Feba was at the club with a friend when the shooting broke out.
"She told me someone was shooting. Everyone was getting on the floor," Feba told the Orlando Sentinel. "I told her I didn't think it was real, I thought it was just part of the music, until I saw fire coming out of his gun."
She was rushed to hospital but died of her wounds.
The Plaza gunman, 27-year-old Kevin James Loibl, then killed himself. His motive remains unknown.