Trump in a social media posting said the strike killed three and was carried out against a vessel "affiliated with a Designated Terrorist Organization conducting narcotrafficking in the USSOUTHCOM area of responsibility".
He did not provide more precise details about the location of the strike.
The Pentagon on Friday deferred questions about the strike to the White House, which did not respond to a request for clarity about the origins of the vessel.
"Intelligence confirmed the vessel was trafficking illicit narcotics, and was transiting along a known narcotrafficking passage enroute to poison Americans," Trump said in the post.
Trump also posted a video of the latest strike that shows a vessel speeding through waters before it appears to be struck by a pair of missiles from overhead and sink in a fiery explosion.
"It was at this moment, the narcoterrorists knew they screwed up," White House communications director Steven Cheung said on X in a posting with the video.
Trump on Monday announced the US military had carried out a strike on a boat allegedly carrying drugs from Venezuela. That strike also killed three on board.
That followed a September 2 military strike on what the Trump administration said was a drug-carrying speedboat that killed 11.
Trump claimed the boat was operated by the Tren de Aragua gang, which was listed by the US as foreign terrorist organisation earlier in 2025.
The Trump administration has justified the military action as a necessary escalation to stem the flow of drugs into the United States.
But several senators, Democrats and some Republicans, as well as human rights groups have questioned the legality of Trump's action.
They view it as a potential overreach of executive authority in part because the military was used for law enforcement purposes.
The Trump administration has yet to explain how the military assessed the boat's cargo and determined the passengers' alleged gang affiliation before the attacks on the vessels.
National security officials told members of Congress that the first boat taken out was fired on multiple times after it had changed course and appeared headed back to shore.
The strikes follow a build-up of US maritime forces in the Caribbean.
It marks a dramatic shift in how the US is willing to combat drug trafficking in the western hemisphere.
In Venezuela, some are speculating whether the strikes are part of a plan to try to topple President Nicolas Maduro, a notion the Venezuelan leader has echoed.
Maduro claimed after the first strike that a US video released by Trump was created with artificial intelligence and that a boat of that size cannot venture into the high seas.
But earlier this week Maduro lashed out at the US, accusing the Trump administration of using drug trafficking accusations as an excuse for a military operation whose intentions are "to intimidate and seek regime change" in the South American country.
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