The son of a tailor, Guglielmo Giraldi was one of the favorite illuminators of Renaissance ruling families, including the Este of Ferrara and the Gonzaga of Mantua. Giraldi worked on a number of important commissions in Ferrara, including a set of choir books for the city's Carthusian monastery and the Bible of Borso d'Este, perhaps the most costly and lavish book in the history of Ferrarese art. Around 1474 Giraldi moved to Urbino, where he worked for Duke Federigo da Montefeltro, illuminating Virgil's Aeneid,Dante's Divine Comedy,and other works.
In his miniatures, Giraldi demonstrated his familiarity with the works of Piero della Francesca and Cosimo Tura, both of whom worked at the Este court. He was one of the pioneers of the new Renaissance style in manuscript illumination in northern Italy.