The complex of Sant'Anna, including the church and a convent, was built in a zone formerly occupied by an unhealthy inlet, circumscribed by cliffs and filled by alluvial deposits of the Kemonia, one of the rivers of the ancient and medieval Palermo. In the period of the Sicilian Vespers the area housed the residence of Joanne De Saint Remy, collaborator of Charles of Anjou.
In the 16th century a chapel dedicated to Our Lady Of Pity is recorded in the so-called “Contrada della Misericordia”. In this chapel Tommaso de Vigilia painted a fresco of the Pietà. Over time the popular devotion to this icon increased. In 1596 a structure located near the chapel and used as granary was converted into a place of worship. The fresco was hung in this new temple. In 1597 the convent was built.
Since the church proved to be small for the liturgical needs, the authorities of Palermo decided to enlarge the building thanks to the help of noble families and ordinary believers. The architectural project was made by the senatorial architect Mariano Smiriglio. On 26 October 1606 the groundbreaking was launched. The church was completed in 1632 and consecrated on 13 November 1639 by the bishop of Agrigento Francesco Traina. The temple was dedicated to Saint Anne, mother of Mary, becoming known as Sant'Anna la Misericordia.
In 1726 the earthquake of Terrasini caused the façade collapse. The current façade was designed by Giovanni Biagio Amico in accordance with the conventions of the Roman Baroque. Over the centuries the church was damaged on several occasions by earthquakes.
After the unification of Italy the church and the convent were confiscated by the state. For several years the complex was used as granary. In 1925 the church and a portion of the convent returned into the possession of the friars.
Today the convent houses a museum of modern art, the Galleria d'Arte Moderna Sant'Anna.
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