The gunman, named by officials as Omar Mateen, was killed after taking hostages.
Another 53 people were injured in the shooting at the Pulse club.
It is the worst mass shooting in recent US history. Florida governor Rick Scott said it was “clearly an act of terror”.
Officials said the killings were likely to be ideologically motivated, though there was no information that the gunman was associated with a particular group.
However, US Congressman Alan Grayson said it was “no coincidence” the attack happened in a gay club.
“It may be we’ve seen the commission of an awful hate crime,” he added.
Mateen’s father Mir Seddique told NBC News that the incident had nothing to do with religion, and may have been triggered by the sight of a gay couple kissing in Miami.
But NBC News reported that Mateen called the emergency services before the attack and swore allegiance to the so-called Islamic State militant group.
French President Francois Hollande condemned the mass killing “with horror” and expressed the “full support of France and the French with America’s authorities and its people in this difficult time”, a statement by his office said.
Meanwhile Pope Francis expressed “deep horror and condemnation” of the “homicidal folly” of the shooting.
It is believed that the suspect, who was a US citizen from the Florida town of Port St Lucie and was of Afghan descent, was not on a terrorism watch list, although he was being investigated for an unrelated criminal act.
The death toll given by Mayor Dyer means that the Orlando attack surpasses the 2007 massacre at Virginia Tech which left 32 people dead.
“Today we’re dealing with something that we never imagined and is unimaginable,” he said, adding that there was “an enormous amount of havoc” and “blood everywhere”.
“Because of the scale of the crime I’ve asked the [Florida] governor to declare a state of emergency,” he said.
“We’re also issuing a state of emergency for the city of Orlando so that we can bring additional resources to bear to deal with the aftermath.”
Security has also been boosted for the last day of the Capital Pride LGBT festival in Washington DC, which will include a moment of silence for the Orlando victims at 13:00 local time.Culled from the bbc.