Pérez Roque was formerly an electronics engineer and leader of student organizations who had served as Fidel Castro's chief of staff for a decade prior to his ministry.

He was replaced as Foreign Minister by former United Nations Ambassador Bruno Rodríguez Parrilla in March 2009 after allegations of expressing scornful words against Fidel Castro's rule and the positions of other senior communist party leaders obtained from covert recording bugs.

He called Cuba a "country under siege" as a result of the US embargo against Cuba Pérez Roque made a series of speeches at the annual United Nations General Assembly gatherings, criticizing the role of the United States and requesting that US troops be withdrawn from Iraq.

[1] Pérez Roque was also responsible for the deepening of trade relations between Cuba and the People's Republic of China,[2] and made a number of high-profile trips to the country, signing a key military agreement between the two nations.

Fidel Castro then criticized him and Carlos Lage Dávila (without naming them) for love of power in a statement on 3 March, and Pérez Roque announced his resignation from all his party and state positions—membership on the Communist Party's Central Committee and Political Bureau, membership on the Council of State, and his role as a parliamentary deputy—in a letter published on 5 March.