The origins of the church date back to the 11th century: a document from 1101 mentions it as a priory under royal patronage of the Abbey of the Most Holy Trinity of Mileto, founded by Count Roger I. This status was also confirmed by a bull of Pope Eugene III in 1150. In 1454 the bishop of Girgenti granted the Congregation of Purgatory the land to build the sacristy. In 1606 the church was assigned to the Confraternity of Purgatory, which restored and expanded it.
A radical restoration, financed in 1711 by the priest Riccobene, completely transformed the building, erasing every trace of the previous structure. In 1747, during the visit of the bishop of Girgenti Lorenzo Gioeni, the church was elevated to parish status and entrusted with the San Francesco district, together with the churches of Santa Croce, the Crucifix, and San Biagio.
In 1806 the interior stuccoes were created, while in 1910, thanks to funds collected by Canon Natale, the façade, the marble high altar, and the statue of Saint Anthony were renewed.
Until the Second World War, the church housed precious works of art, including: a terracotta sketch of Saint John (now in the Diocesan Museum of Caltanissetta), and the Crocifisso dello Staglio, a painting now preserved in the Abbey of Santo Spirito. During the 1943 bombing, the building suffered serious damage and was rebuilt in 1945.
In 2008, the Superintendency of Artistic and Cultural Heritage of Caltanissetta initiated a restoration that involved both the interior (with conservation of stuccoes and paintings) and the exterior, where a new roof with laminated wooden trusses was built. The church stands in the heart of Caltanissetta’s old Arab quarter, among the alleys not far from the Church of San Domenico. The façade, in sandstone and one single order, is surmounted by a triangular pediment and features: a central portal, a niche with the statue of Saint John, and a large window illuminating the interior. On the left rises the bell tower.
The interior, decorated by the painter Pollace, has a single nave with three lateral sections, each with an altar. Among the works preserved are: a statue of the Immaculate Conception by Biangardi, a wooden Saint Joseph from the 18th century, and a painting of Saint Joseph attributed to Pollace. Of particular importance is the baptismal font, considered the oldest in the city.