A gunman, named as 64-year-old Nevada resident Stephen Paddock, opened fire from the 32nd floor of the Mandalay Bay Hotel towards an open-air music festival attended by 22,000.
He killed himself as police stormed the room where 10 guns were found.
He praised the efforts of the emergency services, saying their "miraculous" speed saved lives.
The attack is the worst mass shooting in recent US history.
Las Vegas Sheriff Joe Lombardo described the shooting as a "lone wolf" attack and there was no information about Paddock's motives.
"We have no idea what his belief system was," he said.
So-called Islamic State later claimed to be behind the attack, saying that Paddock had converted to Islam some months ago.
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