Espin earned her revolutionary credentials by joining the armed struggle against Fulgencio Batista, the military ruler, in her hometown of Santiago, on Cuba's eastern coast, in 1956.
Rebelling against her wealthy upbringing - her father was an executive at the Bacardi rum distillery - Espin joined Castro's guerrillas in the Sierra Maestra mountains where she met Raul.
With her brother-in-law in power, Espin helped to establish and then lead the FMC to fight illiteracy and bolster women's political participation, also campaigning on issues such as abortion, contraception and children's rights.
Today, the federation has about 3.6 million members, or 85 per cent of the island's women.
Espin also successfully pushed for the decriminalisation of homosexuality in 1979.
She was one of the first Cuban women to earn a chemical engineering degree, and did graduate studies at the Massachusetts Institute of Technology before joining the revolutionary cause.
A British diplomatic report on leading Cuban personalities in 1967 described Espin as a "strikingly handsome and even attractive woman, who uses much more make-up and other aids than is the revolutionary custom and manages to make even her uniforms smart and feminine".
Espin was a member of the ruling Communist Party's central committee since its creation in 1965.
She was a member of the party's politburo from 1980 until 1991 and remained a member of Cuba's Council of State.
State-run Cuban television said Espin died from complications from a long illness, but did not give further details.
The Cuban government declared one day of official mourning in Espin's honour.