Castro said the 10 changes among senior officials were intended to make Cuba's government more compact and functional and to work toward "perfecting" the Cuban system.
Raul Castro, the Cuban president, has sacked the country's foreign and economic ministers as part of a comprehensive government reshuffle.
Felipe Perez Roque who had been Havana's chief diplomat since May 1999, was replaced by his deputy, Bruno Rodriguez.
Carlos Lage, a vice-president who had far-reaching economic powers, was also removed from his post as executive secretary of the Council of Ministers, but it was not clear whether he would stay on as one of the vice-presidents of the Council of State.
He was replaced as cabinet secretary by General Jose Amado Ricardo Guerra, a former top military official.
Lage had been credited with helping to save Cuba's economy by implementing economic reforms after aid from the Soviet Union ended in the early 1990s.
Perez Roque was once personal secretary to Fidel Castro, Raul's brother and the former president, and a former leader of the Communist Party's youth organisation.
Planned changes
Raul Castro, who took over the presidency in February last year from Fidel, had said for months that he would restructure the government to make it leaner and more responsive.
But Lucia Newman, Al Jazeera's Latin America editor, said: "This is an unprecedented shake up, as never before have so many government officials been replaced in one go."
"It is a new direction, we're just not clear what direction Castro is planning - a return to communist orthodoxy or pragmatism? However, Castro does seem to be trying to put in position people closer to him than to his brother, Fidel."
The ousting of Roque was a particular surprise to many analysts, as he was considered one of the most internationally prominent, and successful, members of Castro's government.
Our correspondent adds that the move could also be a message to the US, just a month before the summit of the Americas in Trinidad where the US could be pressured over its Cuba policies, that Cuba is aiming for change.
Jose Luis Rodriguez, the economy minister, Raul de la Nuez, the minister of foreign trade, and Jose Luis Gacia, the minister of economy and planning, were also removed from their posts.
Georgina Barreiro Fajardo, the finance minister, and Alfredo Morales Cartaya, the labour minister, were also fired.
The ministries of fishing and food were also combined as part of the changes, as were the ministries of foreign investment and foreign trade.
The changes were announced by state television on Monday.
On Monday, Raúl Castro, the President of Cuba, announced several changes of ministers in his cabinet. This is the first major reshuffle since Raúl took over as President after his brother Fidel Castro. A total of twelve ministers were replaced.
Raúl Castro in 2008. 
One of the highest profile changes was Carlos Lage Dávila, the executive secretary of the Council of Ministers, who was replaced by General José Amado Ricardo Guerra. According to senior research associate at the University of Miami, José Azel, Lage was responsible for rescuing the Cuban economy from the downturn that followed the collapse of the Soviet Union in 1991. It was not announced whether Lage will continue to serve in his other position as the vice president of the Council of State of Cuba.

"It looks like Raúl putting some of his own people in," said Wayne Smith, who heads the Cuba program at the Center for International Policy. Smith added that this "is the biggest shake-up that I've seen in a very long time ... for the last 30 or 40 years."

"This is one more sign that Raúl Castro is consolidating his power," José Azel said. "He's putting his people in there."

"It is a new direction, we're just not clear what direction Castro is planning — a return to communist orthodoxy or pragmatism? However, Castro does seem to be trying to put in position people closer to him than to his brother, Fidel," said Al Jazeera's Latin America editor, Lucia Newman.

Among other ministers replaced were foreign minister Felipe Pérez Roque, finance minister Georgina Barreiro Fajardo, labor minister Alfredo Morales Cartaya, and economy minister Jose Luis Rodriguez.