A church at the site was putatively located here by the 4th century, and dedicated to the Conversion of St Paul.
It was originally located outside the Carolingian walls, and facing the former Decumanus maximus, now mainly Via Tornabuoni.
By 1250, it was a collegiate church, and officiated during 1217-1221 by Dominican friars from Santa Maria Novella.
A major reconstruction took place in 1667, when it was decided the church was to be rotated 90 degrees from the prior orientation, under the guidance of the architect Giovan Battista Balatri.
Work was completed in 1693 with contributions by Maestro Francesco Masini for the nave and Messer Bastiano Messeri for the dome.