More than 400 victims were taken to the hospital, authorities said.
SWAT officers using explosives stormed the gunman's hotel room and found he had killed himself, authorities said.
There was no immediate word on the motive for the attack. The U.S. Homeland Security Department said there was no "specific credible threat" involving other public venues in the U.S.
Country music star Jason Aldean was performing Sunday night at the end of the three-day Route 91 Harvest Festival in front of a crowd of 22,000 when the gunman opened fire from inside the Mandalay Bay Hotel and Casino.
The gunman was identified as Stephen Craig Paddock, 64, of Mesquite, Nevada.
SWAT teams quickly descended on the concert and the casino, and officers used explosives to get into the hotel room where the suspect was inside, authorities said.
"What we are going to try to do as best we can is to get our first responders back on their feet and responding and conducting a proper investigation to ensure that we have the safety of this community at heart," Sheriff Joseph Lombardo said.
Aldean was in the middle of a song when the shots came rapidly: Pop-pop-pop-pop. Video of the shooting then showed Aldean stopping and the crowd getting quiet as if it were unsure of what had just happened.
The gunman paused and then fired another volley, the muzzle flashes visible from the casino, as more victims fell to the ground while others fled in panic. Some hid behind concession stands, while others crawled under parked cars.
Kodiak Yazzie, 36, said the music stopped temporarily when the first shots began and the tune even started up again before the second round of pops sent the performers ducking for cover and fleeing the stage.
"It was the craziest stuff I've ever seen in my entire life," Yazzie said. "You could hear that the noise was coming from west of us, from Mandalay Bay. You could see a flash- flash- flash- flash."
As the bullets ran rampant, thousands in the crowd fled in every direction. Couples held hands running through the dirt lot. Faces were brushed with shock and confusion, tears and screams. Some were bloodied and others were carried out by fellow concert-goers.
Monique Dumas from British Columbia, Canada, said she was at the concert, six rows from the stage, when she thought she heard a bottle breaking, and then a burst of popping sounds that may have been fireworks.
She said as she made her way out, it was "organized chaos" as everyone fled. "It took four to five minutes and all that time there was gunfire."
In addition to Paddock, police said they located a woman who may have been his roommate — Marilou Danley, 62. Lombardo said they believe this was a "lone wolf" attack.
"It's a devastating time," Lombardo said.
Police shut down the usually busy Las Vegas Boulevard and authorities across the state and federal ranks converged on the scene as dozens of ambulances ferried those struck by gunfire. Nearby Interstate 15 and flights at McCarran International Airport were briefly closed.
Hospital emergency rooms were jammed with victims delivered by ambulance. Others loaded the wounded into their cars and drove them to hospitals.
Jose Baggett, 31, of Las Vegas, said he and a friend were in the lobby of the Luxor hotel-casino — directly north of the festival — when people began to run, almost in a stampede.
He said people were crying and as he and his friend started walking away minutes later, they encountered police checkpoints where officers were carrying shotguns and assault rifles.
"There were armored personnel vehicles, SWAT vehicles, ambulances, and at least a half-mile of police cars," Baggett said.
Among those killed were two off-duty police officers who were attending the concert. Two on-duty officers were wounded, including one who underwent surgery and was upgraded to stable condition, police said.
Hours after the shooting, Aldean posted on Instagram that he and his crew were safe and that the shooting was "beyond horrific."
"It hurts my heart that this would happen to anyone who was just coming out to enjoy what should have been a fun night," Aldean said.
President Donald Trump tweeted: "My warmest condolences and sympathies to the victims and families of the terrible Las Vegas shooting. God bless you!"
Before Sunday, the deadliest mass shooting in modern U.S. history took place in June 2016, when a gunman opened fire at a gay nightclub in Orlando, Florida, killing 49 people
Sunday's shooting came more than four months after a suicide bombing at an Ariana Grande concert in Manchester, England, that killed 22 people. Almost 90 people were killed by gunmen inspired by Islamic State at the Bataclan concert hall in Paris during a performance by Eagles of Death Metal in November 2015.
An earlier version of this report had an incorrect spelling for the last name of witness Kodiak Yazzie. This story has been corrected to reflect that the officer in critical condition was on duty at the time of the shooting.