The US President said that he had spoken with US military officials who thought the incident in the Lebanese capital's port area seemed to be an attack, "a bomb of some kind."
Speaking at a White House briefing following the blast that killed at least 70 people and injured more than 3,000 others, Mr Trump said the US “stands ready to assist Lebanon”.
He added: “We will be there to help. It looks like a terrible attack.”
Lebanon's interior minister said initial information indicated that highly explosive material, seized years ago and which had been stored at the port, had blown up.
When quizzed by a reporter if he was certain the explosion was in fact an attack, Mr Trump said he had “met with some of our great generals and they seem to feel that it was”.
He continued: “This was not some kind of a manufacturing explosion type of event.
“They would know better than I would.”
Lebanon's President Michel Aoun said that 2,750 tonnes of ammonium nitrate had been stored for six years at the port without safety measures and said it was "unacceptable".
Prime Minister Hassan Diab said in a televised address to the nation there would be accountability for the deadly blast at a "dangerous warehouse".
The explosion also happened amid rising tensions between Israel and the militant Hezbollah group along Lebanon's southern border. Israel denied any responsibility.
Officials said they expected the death toll to rise further after the blast, as emergency workers dug through rubble to rescue people and remove the dead.
It was the most powerful explosion in years to hit Beirut, which is already reeling from an economic crisis and a surge in coronavirus infections.