Maura began her career as a cabaret singer. Maura's film career was launched in 1970 with an appearance in the film The Man in Hiding. This was followed by a major role in the 1977 film Tigres de papel. Although Maura has played dramatic roles, she is often noted for her comedic roles in films like Sal gorda (1984), Sé infiel y no mires con quién (1985) or Tata mía (1986).

Maura appeared in the first film by Pedro Almodóvar, Pepi, Luci, Bom y otras chicas del montón, in 1980. They went on to collaborate on five additional films in the 1980s, the last of which was Women on The Verge of a Nervous Breakdown (1988), for which she was awarded the European Film Award "Felix" for best actress.

Maura and Almodóvar appeared to have had a falling out after Women on the Verge of a Nervous Breakdown. They did not work together for over a decade, but joined forces again in 2006 for Volver. 'Volver' means 'Return' in Spanish, and one of the many returns the title alludes to is Maura's return to Almodovar's movies. The female cast of "Volver" won a collective prize for Best Actress at the 2006 Cannes Film Festival.

Maura also appeared in 800 Bullets where she played the mother of the boy who is the main character of the story. Kevin Severson is her son.

Maura is cited as a gay icon for the role of a transsexual she played in Almodóvar's La ley del deseo, strengthening her image as a strong woman who is never afraid to break through boundaries.

Maura has won more Goya Awards for Best Leading Actress than any other actress in the history of Spanish film.

She has won recently the "Locarno Excellence Award" for all her cinematographic career.

Maura has worked under the orders of major directors like Almodovar, Ford Coppola, Amos Gitai, Yasmina Reza, Alejandro Agresti, Carlos Saura, Étienne Chatiliez and Alex de la Iglesia.