Espín served as a member of the Central Committee of the Cuban Communist Party from 1965 to 1989. She also held many other roles in the Cuban government, including chair of the Commission for Social Prevention from 1967 to 1971, director of Industrial Development in the Ministry of Food in 1969, president of the Institute of Childcare in 1971, and member of the Cuban Council of State in 1976. In addition to her roles within Cuba, Espín also served as Cuba's representative at the United Nations General Assembly.
Espín took on the role of Cuba's First Lady for 45 years, initially taking on the role as the sister-in-law to Fidel Castro, who was divorced at the time he came to power. She officially became the First Lady in 2006 when her husband, Raúl Castro, became president. Additionally, she was granted the title of "Secretary of State" in the Government of Cuba.
Espín headed the Cuban Delegation to the Congress of the International Federation of Democratic Women in Chile in September 1959. She also headed the Cuban delegations to subsequent Conferences on Women, praising them as "invaluable to women in developing countries."