UN High Commissioner for Human Rights Volker Turk called for an investigation into the strikes, in what appeared to mark the first such condemnation of its kind from a United Nations organisation.
Ravina Shamdasani, a spokeswoman for Turk's office, relayed his message on Friday at a regular UN briefing: "These attacks and their mounting human cost are unacceptable.
"The US must halt such attacks and take all measures necessary to prevent the extrajudicial killing of people aboard these boats."
She said Turk believed "air strikes by the United States of America on boats in the Caribbean and in the Pacific violate international human rights law".
President Donald Trump has justified the attacks on the boats as a necessary escalation to stem the flow of drugs into the United States, but the campaign against drug cartels has been divisive among countries in the region.
US defence secretary Pete Hegseth on Wednesday announced the latest US military strike in the campaign, against a boat he said was carrying drugs in the eastern Pacific Ocean.
All four people aboard were killed.
It was the 14th strike since the campaign began in early September, while the death toll has grown to at least 61.
Ms Shamdasani noted the US explanations of the efforts as an anti-drug and counter-terrorism campaign, but said countries have long agreed that the fight against illicit drug trafficking is a law enforcement matter governed by "careful limits" placed on the use of lethal force.
Intentional use of lethal force is allowed only as a last resort against someone representing "an imminent threat to life", she said.
"Otherwise, it would amount to a violation of the right of life and constitute extrajudicial killings."
The strikes were taking place "outside the context" of armed conflict or active hostilities, Shamdasani said.
