A military spokesman said the Iron Duke intercepted the speedboat on July 18 about 110 miles north of Venezuela's and Colombia's coastlines.
William was the lookout on the Lynx helicopter deployed to track the boat as marksmen shot out the vessel's engine. The military said commandos from the Royal Marines aboard the helicopter used high-power, long-range rifles to disable the 30-foot vessel after it tried to evade detection and ignored warning shots.
A British military spokesman said William, second in line to the British throne, was aboard the helicopter as part of his training. He did not take part in the firing, but played "a sort of lookout role," the spokesman said on condition of anonymously in line with military policy.
The military said three Colombians were arrested when the HMS Iron Duke, the British frigate from where the helicopter operates, caught up with the stricken speedboat. But while traces of cocaine were detected on two of the three men, no drugs were found aboard.
The military said the ship was later sunk under the authority of the U.S. Coast Guard team working aboard the Iron Duke. The men were handed to Colombian authorities.
The military has announced the prince's encounter with Caribbean drug traffickers once before. Earlier this month, the Ministry of Defense said William helped his crew mates intercept a speedboat carrying 1,900 pounds (900 kilograms) of cocaine northeast of Barbados.
Both William, 26, and his younger brother Harry -- who was briefly deployed to Afghanistan -- are continuing a family tradition of military service. Their grandfather Prince Philip had a long Navy career, as did their father, Prince Charles, and their uncle, Prince Andrew, flew a Sea King helicopter during the Falklands War.
Although it conducts counter-narcotics operations with the U.S. Coast Guard, the Iron Duke's primary mission is to support Britain's Caribbean territories and provide disaster relief. It is due to remain in the area until October.