A gunman opened fire from the 32nd floor of the Mandalay Bay Hotel toward an open-air music festival being held close by.
Police said a suspect identified as a local resident had been shot and killed by officers.
They said they were looking for a companion travelling with the suspect as a "person of interest".
Hundreds of people fled the scene and the sound of what appeared to be prolonged automatic gunfire could be heard on videos posted on social media.
There had been reports of other incidents at different locations along the Las Vegas strip, but police say they believe the dead suspect acted alone.
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