Originally constructed in 1571 as a parish church under the Archdiocese of Mexico, it became a separate diocese on 6 February 1579 via the Pontifical decree Illius Fulti Præsido by Pope Gregory XIII.

On 27 April 1981, Pope John Paul II raised the shrine to the status of Minor Basilica through his motu proprio Quod Ipsum Manilensis.

[20] The Spanish conquistador, Miguel López de Legazpi chose the church's location and placed it under the patronage of Santa Potenciana.

In 1581, Domingo de Salazar, the first-ever bishop of Manila, constructed a new building made from nipa, wood and bamboo that was consecrated on December 21, 1581, formally becoming a cathedral.

The building was destroyed by a fire that started during the funeral of Governor-General Gonzalo Ronquillo de Peñalosa at San Agustin Church and razed much of the city.

Governor-General Juan Niño de Tabora and his wife Doña Magdalena Saldivar y Medoza built another collateral structure to shelter subsequent relics.

[22] The third cathedral structure, consisting of three naves and seven chapels, was built in 1614, largely using donated funds from the fourth dean Don Francisco Gomez de Arellano.

[23] In 1750, the Florentine friar Juan de Uguccioni added a media naranja ("half orange") dome to the crossing and introduced a transept to the structure.

The fifth cathedral, which closely resembled the Church of the Gesù in Rome, was inaugurated on December 8, 1760;[25] since then, there had been no modifications or alterations to the structure except for some minor repairs.

[27] During the Philippine Revolution of 1896, Archbishop Bernardino Nozaleda y Villa opened the cathedral to Spanish soldiers who sought refuge.

[29] After the Second World War, archbishops Michael J. O'Doherty and Gabriel Reyes planned to transfer the seat of the Archdiocese of Manila to Mandaluyong.

The first cornerstone of the eighth cathedral was blessed and laid by Cardinal Fernando Quiroga Palacios, the Archbishop of Santiago de Compostela and papal legate of Pope Pius XII, on December 8, 1954.

After Cardinal Luis Antonio Tagle assumed his post as Archbishop of Manila in December 2011, one of his first decisions was to close the cathedral.

[9] The year-long celebrations commemorating the 60th anniversary of the Manila Cathedral's post-war restoration began with the opening of a historical exhibit on December 8, 2017.

[45] On October 27, 2018,[46] Pope Francis appointed Cardinal Thomas Aquino Manyo Maeda, then-Archbishop of Osaka, as his papal legate for this occasion.

[47] On December 1, Pope Francis wrote a letter to Cardinal Maeda, calling the cathedral as the "mother and head of the churches" in the Philippines.

The pope further wrote in his letter:[48] "Indeed, this temple which has truly undergone great changes, destroyed seven times by earthquakes and other calamities through the centuries, was diligently rebuilt again and again by the faithful.

[51] Eight bronze panels sculpted by Alessandro Monteleone and Francesco Nagni dominate the central northwest doors of the cathedral.

[52] The tympanum above the central doors bears the Latin inscription Tibi cordi tuo immaculato concredimus nos ac consecramus ("To thy Immaculate Heart, entrust us and consecrate us").

[54] The marble floors on the center aisle near the altar bears the coats of arms of four cardinal archbishops of Manila: Rufino Santos, Jaime Sin, Gaudencio Rosales, and Luis Antonio Tagle.

[56] The restored cathedra bears a carving of the coat of arms of Cardinal Jose Advincula, the present archbishop, imposed on top of white Indian marble.

[55] Manila Cathedral is dedicated to the Blessed Virgin Mary under the title of the Immaculate Conception, who is honored as the Principal Patroness of the Philippines.

[58][59] Inscribed on the baldachin above the statue of the Immaculate Conception is the Latin antiphon Tota pulchra es, Maria, et macula originalis non est in Te ("Thou art all-beautiful, Mary, and the original stain [spot] (of sin) is not in thee").

In 1581, Pope Gregory XIII issued a papal bull consecrating the cathedral building to The Purest and Immaculate Conception of Mary.

[60] The same pope, through "Quidquid ad Dilatandum", reiterated this declaration of patronage on July 16, 1958, through the chancellor of apostolic briefs Gildo Brugnola, who signed and executed the decree.