The 89-year-old confirmed he was stepping down as leader of the Cuban Communist Party in his opening speech of their annual congress on Friday.
Mr Castro, who took over leadership from his late brother Fidel Castro in 2008, has previously indicated he would hand over control as the party’s next secretary-general to President Miguel Diaz-Canel.
"I believe fervently in the strength and exemplary nature and comprehension of my compatriots, and as long as I live I will be ready with my foot in the stirrups to defend the fatherland, the revolution and socialism," Mr Castro said at the Havana convention, according to Reuters.
In anticipation of the announcement, the White House earlier on Friday said a shift in policy on Cuba was not a priority for the administration of Joe Biden.
Press secretary Jen Psaki said while additional steps on Cuba, or US’s sanctions on the country, were not currently in the president’s top foreign policy priorities, they would remain engaged and focused with the country following the change of leadership.
“Our policy as it relates to Cuba is going to be governed by two principles, support for democracy and human rights is going to be at the core of our efforts by empowering the Cuban people to determine their own future,” she said.
“Americans, especially Cuban Americans, are the best ambassadors for freedom and prosperity.”
The outgoing Trump administration added Cuba to its list of state sponsors of terrorism during the final weeks of its presidency in January.
Analysts had predicted that the Biden administration would reverse the decision, which blocked efforts that began during the Obama administration to re-open and normalise relations with Cuba.
Former Secretary of State Mike Pompeo accused Cuba of "repeatedly providing support for acts of international terrorism in granting safe harbour to terrorists”.