The prime minister offered his prayers to the families of the more than 50 victims and wished the 500-plus injured a swift recovery.
"We stand with you and we mourn with you in this difficult time," Mr Turnbull told a maritime defence conference in Sydney on Tuesday.
"This was a cruel and callous attack on innocent people at a concert."
It was the worst mass shooting in America's history at the hands of 64-year-old Stephen Paddock."
This is a reminder that we must constantly work to stay ahead of the threat - whether the motives of those who seek to do us harm," Mr Turnbull said.
He noted the government released in August its new strategy to protect crowded places so that Australians could go to events like concerts without fear of being harmed.
With the Las Vegas massacre reigniting debate about gun laws in the US, Mr Turnbull acknowledged that thanks to the strong leadership of John Howard more than 20 years ago after the Port Arthur massacre, Australia has some of the strictest gun control laws in the world.
"And we remain ever vigilant to maintain them," he said.
Australia just completed another national gun amnesty, with more than 25,000 weapons surrendered.
State and territory leaders will also meet on Thursday for a special national security summit.
"We must constantly improve our laws and our techniques to stay ahead of those who seek to do us harm."
Opposition Leader Bill Shorten described the scenes out of Las Vegas as horrifying.
"Australians holding our American friends in our hearts tonight," he tweeted.
It's not know whether any Australians were hurt in the attack.
"If you have any concerns for the welfare of family and friends in the Las Vegas area, you should attempt to contact them directly," a Department of Foreign Affairs and Trade spokeswoman told AAP.
No Australians have been identified at this stage as victims of the Las Vegas shooting massacre, Foreign Minister Julie Bishop says.
"We know that a number of Australians were in the vicinity or are in the vicinity, but at this stage and the situation is evolving, no Australians have been identified amongst the victims or those injured," she told Nine.
People unable to make contact with loved ones should phone the DFAT emergency hotline: 1300 555 135, or +61 2 6261 3305.
Meanwhile, Las Vegas police said they had cleared Marilou Danley, 62, reportedly an Australian and the gunman's girlfriend, of any involvement.