The museum occupies a large part of the Dominican convent of San Marco and preserves its atmosphere intact. Founded in 1436 and designed by the architect Michelozzo, the convent played an important role in the religious and cultural life of the city, as evidenced by the story of Friar Girolamo Savonarola, who made it his headquarters.

The museum’s fame is due above all to the paintings of Beato Angelico, one of the greatest painters of the Renaissance, who frescoed many of the convent’s spaces. Among his main works are The Annunciation—a masterpiece of Renaissance painting—The Deposition, The Triptych of St. Peter Martyr, The Annalena Altarpiece, The Last Judgment, The San Marco Altarpiece, The Madonna and Child, and The Tabernacle of the Linen Weavers.
Also notable is the collection of 16th-century works, which includes paintings by, among others, Fra Bartolomeo.