The church of Mater Domini, with a central plan, was built by the the master engineer Michele Profilo between 1605 and 1606. The church was constructed with funds collected from the nobles of Mesagne, Pietro Resta and Nicola Capodieci, supported by Pompeo Falcone from the working-classes. The collection of the funds to build the church lasted from 1558 to 1606 and once the required sum was achieved the work started with the demolition of a chapel in which there was a miraculous fresco of the Virgin with Child.

The church is mentioned for the first time in the pastoral visit of 1606 by the Monsignor Giovanni Falces, on which occasion the archbishop authorised the dismantling of the beams in the roof of the church of Santa Maria in Betlem and their use as scaffolding in the new church being built. The church of Mater Domini, not having an income, was affiliated by archbishop Falces to the episcopal refectory and subsequently, in 1688, the confraternity degli Schiavi di Maria (Servants of Mary) took up office. This confraternity, formed exclusively of farmers, had the merit of funding the building of the vault and the cupola, erected between 1711 and 1715, with their own money.

In 1731, the Regio Tavolaro (royal engineer or architect) Pietro Vinaccia gave an accurate description of the church from which one can deduce that the work had not been finished. We know that the work on the cupola was finished in 1740 during the time of the archpriest Antonio Morranza.

The sanctuary, in the form of a Greek cross, with its geometric forms is different from other buildings of the period. The tripartite facade has a central portal surmounted with a tympanum which hosts a fresco of the Virgin with Child.

At the sides of the portal there are two recesses with statues that come from the monastery of the PP Cappuccini. On the central half pilasters on the upper order there are two sculptures of angels and in line with the portal, there is a glass window. The two orders in the Ionic style are surmounted by an apex in which the letters A-M are written “Ave Maria”.

Inside, in addition to the main altar, there are another four altars on the sides of the transept. On the main altar we find the fresco of the Virgin with Child, probably of Byzantine origin, extensively restored by the painter Gian Pietro Zullo in 1606.

Of note in the north apse is the painting of the Assumption of Mary from the middle of the XVIII century (unknown artist), the tondo with Giuditta and Oloferne (Judith and Holofernes) and the large canvas of the Incredulity of Saint Thomas; attributed to the Mesagnese painter Gian Pietro Zullo dating from 1598. In the south apse there is the Annunciation, again from the middle of the XVIII century (artist unknown), the statue of the Madonna di Mater Domini, and the canvas of the Deposizione (the Entombment of Christ) from the middle of the XVII century.