St. Dominic was born at Calaruega, in Spain, in 1170 and studied theology. He drew attention to himself while on a mission to France when a large number of heretics were converted after having listened to him preach. In 1215 he founded a community of preaching friars in Toulouse and shortly afterwards travelled to Rome (this was when he apparently met St. Francis), where the Pope gave him permission to found a new Order which was to have the function of "custodian of the Catholic Dogma". This function is explained very well inside Santa Maria Novella by the frescoes in the great Spanish Chapel. In 1220 St. Dominic retired to Bologna, where he died the following year. Meanwhile Dominican convents were being founded all over Europe. A small delegation of monks, composed of the Blessed Giovanni of Salerno and twelve brethren, first came to Florence in 1219: two years later the canons of the Cathedral assigned them the area where the convent and later the new Basilica were to be built.

The preaching of the Dominicans became so popular with the Florentines that the square in front of the church had to be enlarged twice, in 1245 and in 1287, and in particular during the period in which St. Peter Martyr from Verona (1205-1252) was in the city; this monk, a wonderful orator and swayer of crowds, was later murdered for vendetta by two killers who had been paid by the Venetian aristocracy. He, as well as the great Dominican philosopher St. Thomas Aquinas, can be seen in several of the frescoes inside the Basilica.