In a post on social media, Hegseth asserted that the "vessel was trafficking narcotics" and those aboard were "narco-terrorists."
He said the strike killed four men but offered no details on who they were or what group they belonged to, following the US designation of several Latin American cartels as foreign terrorist organisations.
President Donald Trump said in his own social media post that the boat was "loaded with enough drugs to kill 25 TO 50 THOUSAND PEOPLE" and implied it was "entering American Territory" while off the coast of Venezuela.
It is the fourth deadly strike in the Caribbean and the latest since revelations that Trump told lawmakers he was treating drug traffickers as unlawful combatants and military force was required to combat them. That assertion of presidential war powers sets the stage for expanded action and raises questions about how far the administration will go without sign-off from Congress.
"Blowing them up without knowing who's on the boat is a terrible policy, and it should end," said Republican Senator Rand Paul of Kentucky, a consistent and harsh critic of the US strikes.
"The President determined that the United States is in a non-international armed conflict with these designated terrorist organisations," according to a memo sent to Congress. Trump directed the Pentagon to "conduct operations against them pursuant to the law of armed conflict," the document says.
Senator Jim Risch, Republican chairman of the Senate Foreign Relations Committee, said the president had the authority to go after the cartels without further authorisation from Congress under "his general powers under the Constitution as the commander in chief."
Paul said only Congress has the authority to declare war and characterised the memo as "a way to pretend like" the administration is notifying lawmakers with a justification for the strikes.
Hours after Hegseth announced the latest strike, Venezuelan Vice President Delcy Rodríguez said the "warlike aggression" by the US affects the greater Caribbean, not just Venezuela.
"We see it and feel it, as they murder our countries' citizens in summary extrajudicial executions," she said during a conference in Venezuela's capital, Caracas, focused on colonialism in the West.
Meanwhile, President Nicolás Maduro did not explicitly mention the strikes, but he told conference attendees that his country is ready to defend itself.
"Venezuela has the right to peace, to sovereignty, to existence, and no empire in this world can take it away," he said. "And if it is necessary to move from an unarmed struggle to an armed struggle, this people will do so. … Colonialism no more."
Colombian President Gustavo Petro, a leftist leader who has clashed with the Trump administration, accused the US of committing "murder" and urged the victims' families to "join forces."
"There are no narco-terrorists on the boats," he posted on X after the strike was announced. "Drug traffickers live in the US, Europe and Dubai. On that boat are poor Caribbean youth."
Video of Friday's strike posted online showed a small boat moving in open water when it suddenly explodes, with water splashing all around it. As the smoke from the explosion clears, the boat is visible, consumed with flames, floating motionless on the water.
The strikes followed a buildup of US maritime forces in the Caribbean unlike any seen in recent times.
