Domenico Puligo came from a family of blacksmiths. His father, Bartolomeo, was a blacksmith and a descendant of the Ubaldini of Marradi in Tuscan Romagna, who were also blacksmiths. His mother was Apollonia, daughter of the goldsmith Antonio di Giovanni. Puligo also had a sister named Francesca. In the early 15th century, the Ubaldini family moved to the village of Ponte a Rifredi on the edge of Florence from their native area. Several years later, the family moved again to the Piazza di San Gallo, resting on the periphery of Porta San Gallo. Here the family lived in a small house that was part of the property of the Spedale di San Gallo.
