She was born to a former cavalry officer and Member of Parliament, Stamatis Mercouris, and his wife Eirini Lappa. When she completed her secondary education, she attended the National Theatre’s Drama School. She graduated in 1944.
As an actress she made her film debut in Stella (1955) and met international success with her performances in Never on Sunday, Phaedra, Topkapi, and Promise at Dawn. She won the award for Best Actress at the 1960 Cannes Film Festival, and she was also nominated for an Academy Award, a Tony Award, three Golden Globe Awards, and two BAFTA Awards.
A political activist during the Greek military junta of 1967–1974, she became a member of the Hellenic Parliament in 1977 and the first female Minister for Culture of Greece in 1981. Mercouri was the person who, in 1983, conceived and proposed the programme of the European Capital of Culture, which has been established by the European Union since 1985.
Mercouri commissioned a study for the integration of all the archaeological sites of Athens to create a traffic-free archaeological park to promote the Greek culture. She introduced free access to museums and archaeological sites for Greek citizens, organized a series of exhibitions of Greek cultural heritage and modern Greek art worldwide, supported the restoration of buildings of special architectural interest and the completion of the Athens Concert Hall, backed the project of the Museum of Byzantine culture in Thessaloniki and established annual literary prizes.