The town of Santa Ana was first established by the Spanish Franciscan missionaries in 1578, in a settlement beside a creek connecting to the Pasig River, which the local inhabitants referred to as Sapà.

[4] However, the construction came only around 1720 upon the direction of then parish priest of Santa Ana, Vicente Inglés, wherein a new site was chosen, which is the current location of the structure.

[7] The church structure follows the Baroque architectural style, utilizing adobe blocks in its wall surface finish to give an impression of massiveness.

The topmost level or the pediment is adorned with Vitruvian-scroll design on its raking cornice, and a central niche flanked with octagonal windows.

[5] Attached to the right side of the structure next to the church facade is the four-floored octagonal bell tower, also made of adobe blocks and were embellished by heavy string courses and other ornamentation.

[5] The tabernacle or sagrario occupied the central niche at the lower level and is flanked by Franciscan saints, namely Bonaventure, Peter of Alcantara, Bernardino of Siena and Clare of Assisi.

The upper level niches contained the images of Anne (the titular patron saint of Santa Ana district) at the center with Peter and Paul on its sides.

Sixteen paintings depicting Jesus, the Twelve Apostles (with Matthias replacing Judas Iscariot), the Four Evangelists; Mark and Luke, and John decorate the first level balcony.

[5] The Camarín de la Virgen (Dressing Room of the Virgin) is a small chapel located behind the niche of Our Lady of the Abandoned on the second tier of the retablo.

Below the hornacina is a semicircular gilded platform, which is said to be a part of the galleon that brought the image from Valencia all the way to Manila, the Santo Cristo de Burgos.

[11] Located behind the Santa Ana Church is the Capillita de la Virgen del Pozo (Small Chapel of the Virgin of the Well).

[12] The Pozo de la Virgen also enshrines an 18th-century wood and ivory relief image of Our Lady of the Abandoned,[12] placed in a low niche in a position suggesting her guarding the holy well.

Above the cloister is a wooden corridor with capiz and glass windows and high doors leading to the priest's quarters, the choir loft and a room previously used as a library.

[5] In 1966, archaeological excavations have been conducted by the National Museum of the Philippines on the patio and the churchyard, uncovering 71 human burials dating around late 11th to 14th centuries from the associated Chinese ceramics recovered with the graves.

[16] The Santa Ana Site Museum located in the convent patio and the Camarín de la Virgen was declared as a National Cultural Treasure in August 1973.