A gunman -- named Stephen Paddock -- opened fire on more than 10,000 concert-goers at an outdoor venue from across the Mandalay Bay hotel at around 10.08 p.m. local time (0500 GMT Monday), Clark County Sheriff Joseph Lambardo from the Las Vegas Metropolitan Police Department (LVMPD) told reporters.
Lambardo referred to the 64-year-old attacker, who was killed by officers on the 32nd floor of the hotel, as a Las Vegas local resident and made no references to terrorism, instead calling the shooting a "lone wolf" attack.
The shooter fired as many as 600 rounds in six or seven bursts with an automatic weapon for nearly four-and-a-half minutes, media reports quoted police sources as saying.
Video footage of the shooting showed thousands fleeing the venue in panic, causing stampedes, according to eyewitnesses.
Police believe there are no additional suspects but are looking for a female "companion" of the shooter, identified as 63-year-old Marilou Danley.
An FBI-assisted investigation is underway, Lambardo said.
An exact number of casualties was not immediately available, officials said. A spokesman for a nearby hospital said at least 12 people were in critical condition.
At least two off-duty police officers are believed to be among those slain, according to media reports.