At least 50 people have been killed after a gunman opened fire on crowds at an outdoor music festival in Las Vegas.

More than 200 others were injured in the mass shooting near the Mandalay Bay Hotel and Casino on the Nevada city's famous gaming strip.

At least two off-duty police officers were killed in the attack, the deadliest mass shooting in US history.

The "lone wolf" attacker is thought to have gunned down crowds at the Route 91 Harvest country music festival from the hotel's 32nd floor, where he was later shot dead by police.

Footage showed terrified concert-goers screaming as they fled automatic gunfire and cowered behind barriers for safety.

Witnesses reporting hearing a noise "like firecrackers" before realising a shooter was unloading "clip after clip" into the crowd.

Others reported seeing muzzle flashes from the upper floors of the Mandalay Bay Hotel and Casino across Las Vegas Boulevard towards festival.

Two off-duty police officers are thought to have been among the dead.

Police placed the area on lockdown and closed off parts of the Las Vegas Strip and Interstate 15.

Some officers took cover behind their vehicles while others carrying assault rifles ran into the hotel.

"Confirming that one suspect is down," tweeted Las Vegas Metropolitan Police Department. "This is an active investigation. Again, please do not head down to the strip at this time."

They later added: "At this time we do not believe there are any more shooters."

Reports on social media, citing police scanners, said a gunman on the 32nd floor of the hotel had also shot at a bodyguard and police.

People carry an injured person at the Route 91 Harvest country music festival (Getty Images) (Getty)

The gunman was as a local Las Vegas man, police have said.They said they knew the identity of the suspect but would not yet name him.

According to unverified reports by ABC News, he was a 64-year-old white male. NBC News named him as Stephen Haddock and he had a criminal record.

A hunt was underway for a 62-year-old female companion of the shooter called Marilou Danley, who they said lived with him and had been travelling with him. Authorities said she was "sought for questioning" and urged anyone who saw her to call 911.

Sheriff Joseph Lombardo described the shooter as a "lone wolf type actor".

"Right now we believe he is the sole aggressor at this point and the scene is static. We are attempting to locate the person of interest," he added.

Two off-dury officers who had been attending the festival are thought to have died, the sheriff said.

Las Vegas Metropolitan Police Department told people to avoid Las Vegas Strip and put the area on lockdown following the shooting.

Police officers and medical personnel stand at the scene of a shooting near the Mandalay Bay resort and casino on the Las Vegas Strip. (John Locher/AP)

Las Vegas City Hall tweeted: "Please avoid the south end of the Strip. Very sad night for Las Vegas."

Witnesses said country singer Jason Aldean was playing near the end of the festival when gunfire rang out.

Kodiak Yazzie, 36, said he and his girlfriend were watching the performance when he heard what sounded like fireworks. The music stopped temporarily and started up again before another round of pops sent the performers ducking for cover and fleeing the stage.

Thousands fled as bursts of gunfire could be heard for more than five minutes, Mr Yazzie said.

Witnesses said they saw multiple victims and dozens of ambulances near the concert venue. Some attendees later huddled in the basement of the nearby Tropicana hotel-casino.

Las Vegas police run by a banner on the fence at the Route 91 Harvest country music festival grounds after shots were fired (David Becker/Getty)

As casualties mounted, the festival’s first aid station became "completely flooded" with wounded, one first responder said.

He told Sky News he saw "multiple people hit, a lot of people shot".

"I myself, with others, carried at least four or five people to the area," he added. "Two people, I know for sure, had been trampled [in the rush to escape.]

"One gentleman was shot in the top of the head, another gentleman shot in the leg. One lady shot in her side, another lady got a round to the side of the head. It was an ugly scene."

MGM Resorts, which owners the hotel where the shooter opened fire, said its "thoughts and prayers are with the victims of last night's tragic events".

It added hotels on the resort were on lockdown at the request of police.

McCarran International Airport, about two miles away, grounded all planes and diverted some incoming flights after reports of the shootings emerged.