In 1406 he was enrolled in the Guild of Masters of Stone and Wood. Between 1407 and 1408 he worked with his father on the cornice of the Porta della Mandorla in S. Maria del Fiore. In 1408 he was commissioned, together with his father, to execute a statue of Isaiah for the façade of the same church, and then, alone, also for S. Maria del Fiore, he made a statue of St. Luke completed in 1413. In 1414 he was entrusted with carving the pediment of the Porta della Mandorla, a work he continued until the year of his death (1421). Other sculptures by him include the statues of St. Philip, St. Eligius, and the Four Crowned Martyrs in Orsanmichele, and a relief image of a prophet on a panel on the exterior of the same building.
Nanni, certainly gifted like few other sculptors of his time, especially in the formidable image of St. Luke, his masterpiece, shows that he understood the spirit of the new age and knew how to look to the art of Donatello, a few years his junior, and of Jacopo della Quercia; yet he did not for this reason renounce his own austere vision of form, strongly articulated in plastic values sometimes simplified with an almost harsh taste (Four Crowned Martyrs), at other times underscored by flowing, undulating lines to mark the boundaries between shadow and light (pediment of the Porta della Mandorla). — See pl. CVI.