Baldovinetti is presumed to have been an assistant to Domenico Veneziano, whose influence is reflected in the clear, pervasive light of his earliest surviving works: “The Baptism of Christ,” “Marriage at Cana,” and “The Transfiguration” (Museo di San Marco, or Museo dell'Angelico, Florence). Baldovinetti was also greatly influenced by Fra Angelico (Angelico, Fra) and Andrea del Castagno (Castagno, Andrea del), with whom he collaborated on the last fresco cycle in the high chapel of Sant'Egidio. He achieved his fully mature style in his masterpiece, “The Nativity” (1460–62), a fresco in the Church of SS. Annunziata, Florence. Although Baldovinetti's technical experiments led to the fresco's rapid decay, it shows the pale colours, atmospheric light, and integration of detail with large-scale design that characterized most of his later works, such as “Madonna and Child” (c. 1465; Louvre, Paris). Both “The Nativity” and “Madonna” include views of the Arno River valley and are among Europe's earliest paintings of actual landscapes.

Baldovinetti also did two strips of mosaic decoration over Lorenzo Ghiberti's doors on the Baptistery in Florence (1453–55) and a St. John the Baptist over the south doorway of Pisa Cathedral (1462). He also prepared designs for intarsias, or wood inlays, and for stained glass.