US President Barack Obama and Pope Francis on Sunday led the condemnation after a gunman went on the rampage at a gay nightclub in Florida leaving at least 50 people dead. The pontiff condemned the killings as "homicidal folly and senseless hatred" while Obama described them as "an act of terror and an act of hate".
The attack in which a gunman opened fire at a packed nightclub in Orlando, Florida, is the worst mass shooting in US history.
Leaders from countries shaken by recent jihadist attacks, including France and Belgium, were among the first to express solidarity with the US.
Afghan President Ashraf Ghani sent his condolences to the families of the victims as authorities identified the alleged gunman as 29-year-old Omar Mateen, a US citizen of Afghan descent. Reacting to the latest in a litany of mass gun killings in the US, Obama said the FBI was "appropriately investigating this as an act of terrorism".
"Although it's still early in the investigation, we know enough to say that this was an act of terror and an act of hate," he said, later ordering flags at half-staff as an act of mourning.
In a statement from the Holy See, Pope Francis lamented the tragic loss of life.
The attack had "caused in Pope Francis, and in all of us, the deepest feelings of horror and condemnation... before this new manifestation of homicidal folly and senseless hatred", said the statement.
"We all hope that ways may be found, as soon as possible, to effectively identify and contrast the causes of such terrible and absurd violence," it added.
"Deeply saddened by the loss of so many innocent lives in Orlando shooting. We join families in their grief," he said.