|Donatello's statue outside of the Uffizi Galleria.|
In Florence, Donatello assisted Lorenzo Ghiberti with the statues of prophets for the north door of the Florence Baptistery, for which he received payment in November 1406 and early 1408. In 1409–1411 he executed the colossal seated figure of Saint John the Evangelist, which until 1588 occupied a niche of the old cathedral facade, and is now placed in a dark chapel of the Duomo. This work marks a decisive step forward from late Gothic Mannerism in the search for naturalism and the rendering of human feelings. The face, the shoulders and the bust are still idealized, while the hands and the fold of cloth over the legs are more realistic.
In 1411–1413 Donatello worked on a statue of St. Mark for the church of Orsanmichele. In 1417 he completed the St. George for the Confraternity of the Cuirass-makers. The elegant St. George and the Dragon relief on the statue's base, executed in schiacciato (also known as bas-relief or basso rilievo) is one of the first examples of central-point perspective in sculpture.
From 1423 is the St. Louis of Toulouse, now in the Museum of the Basilica di Santa Croce. Donatello had also sculpted a tabernacle for this work, but it was sold in 1460 to house the Incredulity of St. Thomas by Verrocchio.
Between 1415 and 1426, Donatello created five statues for the campanile of Santa Maria del Fiore in Florence, also known as the Duomo. These works are the Beardless Prophet; Bearded Prophet (both from 1415); the Sacrifice of Isaac (1421); Habbakuk (1423–1425); and Jeremiah (1423–1426); which follow the classical models for orators and are characterized by strong portrait details. From the late teens is the Pazzi Madonna relief in Berlin. In 1425, he executed the notable Crucifix for Santa Croce; this work portrays Christ in a moment of the agony, eyes and mouth partially opened, the body contracted in an ungraceful posture.
Between 1425–1427, Donatello collaborated with Michelozzo on the funerary monument of the Antipope John XXIII for the Battistero in Florence. Surely by Donatello is the recumbent bronze figure of the deceased, under a shell. In 1427, he completed in Pisa a marble panel for the funerary monument of Cardinal Rainaldo Brancacci at the church of Sant'Angelo a Nilo in Naples. In the same period, he executed the relief of the Feast of Herod and the statues of Faith and Hope for the Baptstery of San Giovanni in Siena. The relief is mostly in stiacciato, while the foreground figures are done in bas-relief.