The historian Cataldo Antonio Mannarino, in his History of Mesagne from 1596, tells us about the Chiesa di Santa Maria della Misericordia. We learn that the church was part of the Mesagne Chapter, of recent construction, but still not completed. In 1638, the archbishop Francesco Surgente visited the church, and without giving detailed information, stated that the church was finished and in a good state. A few years later, in 1643, the pastoral visit by archbishop O’Driscol found the main altar in good condition and the other altar decorated with a picture of the Beata Vergine del Santissimo Rosario (Our Blessed Virgin of the Rosary). The church was regularly visited by various archbishops in the following decades but there is no mention of any particular instructions or orders. The Regio Tavolario (royal engineer or architect) Pietro Vinaccia also mentioned the church in 1731, describing it as having three aisles with a main altar in wood and a picture of Santa Maria della Misericordia (Our Lady of the Mercies). In 1868 the two lateral aisles collapsed, leaving only the surviving central aisle which still exists today.

Worth highlighting in the simple interior of the building are the emblems of the university of Mesagne with low reliefs on the sides, possibly depicting those who commissioned the work, and a coat of arms of the Castriota-Musachi family.