"My warmest condolences and sympathies to the victims and families of the terrible Las Vegas shooting. God bless you!" he wrote.
The shooting, late on Sunday evening at a country music festival close to the city's casino strip, left more than 200 injured. The US President tweeted his condolences around five hours later, at just gone 7am, Washington DC time.
White House spokeswoman Sarah Huckabee Sanders said Mr Trump had been "briefed on the horrific tragedy in Las Vegas".
Ms Sanders said that "we are monitoring the situation closely and offer our full support to state and local officials. All of those affected are in our thoughts and prayers".
Mr Trump is due to visit the storm-ravaged US territory of Puerto Rico on Tuesday, having engaged in a public spat with officials on the island after they accused him of inaction following devastation caused by Hurricane Maria.
There has been no comment from the White House on whether that trip will be rearranged in the wake of the Las Vegas massacre.
Following the attempted bombing of a Tube train at Parsons Green station in London last month, Mr Trump tweeted that it was an attack by a “loser terrorist” and called on authorities to be “proactive”.
Police in Las Vegas have said they are not treating the mass shooting as an act of terrorism, despite Nevada state law defining terror as “any act that involves the use or attempted use of sabotage, coercion or violence which is intended to cause great bodily harm or death to the general population”.
Theresa May and Boris Johnson were among the first world leaders to respond to the killing.
The Prime Minister said her thoughts were with the victims and emergency services following the "appalling attack".
The Foreign Secretary said he was "horrified" by the shooting, adding: "The United Kingdom stands with the American people against this indiscriminate violence. My thoughts are with all those caught up in it.
"The Foreign and Commonwealth Office is in contact with Las Vegas authorities to establish whether any British people were caught up in the attack and we are ready to help however we can."
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