The US Southern Command alleged the vessel struck on Friday was operated by "Designated Terrorist Organisations" that it did not identify.
It said that no US military forces were harmed. It described those killed as "male narco-terrorists," without offering details.
"Intelligence confirmed the vessel was transiting along known narco-trafficking routes in the Eastern Pacific and was engaged in narco-trafficking operations," the US Southern Command said on X.
A 16 second-long clip released by the Southern Command showed a vessel being struck in the waters.
The US military has made numerous such deadly strikes in the eastern Pacific in recent weeks.
President Donald Trump's administration has been striking vessels that it accuses of transporting narcotics.
The US military's strikes on such vessels have killed more than 170 people since September.
Experts and human rights advocates, both in the US and globally, have questioned the legality of the strikes.
Human Rights Watch and Amnesty International have said the strikes amount to "unlawful extrajudicial killings."
The American Civil Liberties Union has cast the assertions by the Trump administration against those it targets as "unsubstantiated, fear-mongering claims."