In statement posted on X, the ministry said the Florida-registered vessel – with the registration number FL7726SH – was detected near Cayo Falcones, in the country’s central Villa Clara province on Wednesday morning.
When a Cuban boat carrying five members of the ministry’s border guard approached the vessel for identification, “the crew of the violating speedboat opened fire” and wounded the Cuban commander, the statement said.
“As a consequence of the confrontation, as of the time of this report, four aggressors on the foreign vessel were killed and six injured.”
Those injured were evacuated and given medical assistance.
The BBC has contacted the US State Department and White House for comment.
Florida Congressman Carlos Gimenez, a Cuban-American former mayor of Miami, said he would demand an investigation into what he called a “massacre”.
He added that US authorities “must determine whether any of the victims were US citizens or legal residents”.
The incident comes amid increased tensions between the US and Cuba, which is facing a deepening fuel crisis that has been worsened by the US blocking oil shipments from Venezuela, a long-standing ally in the region, to the island.
The Cuban statement alluded to these tensions, saying that “in the face of current challenges, Cuba reaffirms its determination to protect it territorial waters” and safeguard its sovereignty.
The incident also comes as US Secretary of State Marco Rubio arrives in Saint Kitts and Nevis to meet with Caribbean leaders amid the Trump administration’s push to ramp up pressure on Cuba’s government, as well as other regional issues.
It also happened one day after Cuban-American groups in Miami commemorated the 30th anniversary of the Brothers to the Rescue shootdown, which killed four people.
Wednesday’s incident sparked several Florida lawmakers to call for an investigation and to criticise the Cuban government.
Florida Congresswoman MarÃa Elvira Salazar said on social media she was following the situation and “awaiting further details from US authorities”.
James Uthmeier, Florida’s attorney general, said he would direct local law enforcement to investigate the incident.
“The Cuban government cannot be trusted, and we will do everything in our power to hold these communists accountable,” he said.
In the US Senate, Florida Republican Rick Scott, demanded “a full investigation into this deeply concerning situation and to determine what happened.”
“The Communist Cuban regime must be held accountable!” he added.