A friend of the poet Federico García Lorca, she was forced into exile during Francisco Franco's dictatorship of Spain, but continued her work in the United States.

Notable plays in which she appeared include Como tú me deseas, La casa de Bernarda Alba, and Mariana Pineda.

An opera, Ainadamar, by the composer Osvaldo Golijov and playwright David Henry Hwang, based on Xirgu's life and her association with Lorca, was premiered in 2003.

In 1911 Àngel Guimerà wrote La reina jove for her, and that year she created her own theater company.

In 1988 the Catalan government repatriated her remains, which are now buried in her native town of Molins de Rei.