Sunday's attack brought the death toll to at least 157 people since the Trump administration began targeting those it calls "narcoterrorists" in small vessels in early September.
As with most of the military's statements on the more than 40 known strikes in the Eastern Pacific Ocean and Caribbean Sea, US Southern Command said it targeted alleged drug traffickers along known smuggling routes.
The military did not provide evidence that the vessel was ferrying drugs. It posted a video on X that showed a small boat being blown up as it floated on the water.
President Donald Trump has said the US is in "armed conflict" with cartels in Latin America and has justified the attacks as a necessary escalation to stem the flow of drugs into the United States.
But his administration has offered little evidence to support its claims of killing "narcoterrorists".
In a meeting with Latin American leaders on Saturday, Trump encouraged them to join the US in taking military action against drug-trafficking cartels and transnational gangs, which he said pose an "unacceptable threat" to the region's national security.
To that end, Ecuador and the US conducted military operations this past week against organised crime groups in the South American country.
With Saturday's gathering, Trump aimed to demonstrate that he remains committed to focusing US foreign policy on the Western Hemisphere, even while waging a war on Iran that has had repercussions across the Middle East.
Critics have questioned the overall legality of the boat strikes as well as their effectiveness, in part because the fentanyl behind many fatal overdoses is typically trafficked to the US over land from Mexico, where it is produced with chemicals imported from China and India.
The boat strikes also drew intense criticism following the revelation that the military killed survivors of the very first boat attack with a follow-up strike.
The Trump administration and many Republican lawmakers said it was legal and necessary, while Democratic lawmakers and legal experts said the killings were murder, if not a war crime.
