When the parish of Dumaguete was founded in 1620, the settlement was a modest pueblo whose jurisdiction stretched across southeastern Negros and the island of Siquijor. Eight secular priests served the parish in its earliest years, beginning with Fr. Juan de Roa y Herrera. For decades, the community worshiped in simpler structures while the threat of coastal raids shaped daily life. The stone church came later, constructed between 1754 and 1776 under Fr. Jose Fernandez de Septien. But Septien built more than a church. He erected four watchtowers at the corners of the church lot, designed to spot and repel Moro raiders attacking from the south. The watchtowers turned the church grounds into a defensive perimeter, transforming a place of worship into an early warning system. In this corner of the Visayas, a church had to double as a fortress.

On November 25, 1846, during the town fiesta, a firecracker ignited a blaze that consumed the church's wooden ceiling, its altars, pews, religious articles, and organ. Only the connected convent survived, saved by townspeople who rushed to contain the fire before it could spread beyond the church walls. The loss was enormous, but the stone shell endured. The decades that followed brought wave after wave of restoration, each priest adding his own layer to the building's history. Fr. Antonio Moreno replaced sacred vestments in the 1860s and installed galvanized roofing alongside the construction of a local children's school built of stone. Fr. Juan Felix de Encarnacion renovated the flooring with fine wood and mounted a bell tower on one of the watchtowers between 1867 and 1879. Fr. Mariano Bernad completed the portico in 1885 and dedicated two side altars to the Virgen de Consolacion and Saint Joseph the following year. By 1891, the interior was fully painted, adorned with embellishments, and fitted with a new organ imported from Zaragoza, Spain.

Of the four original watchtowers, only one survives -- the southeastern tower, fitted with a belfry in 1879 and known as the Campanario. It stands detached from the main church, a coral-stone sentinel that once rang warnings of approaching Moro fleets during the Spanish-Moro conflict. Today the Campanario is recognized as one of the oldest heritage landmarks in Central Visayas. In November 2023, the Commission on Church Cultural Heritage announced the installation of an Important Cultural Property marker at the tower. The following year, the National Museum of the Philippines allocated nine million pesos for its conservation, a joint project with the Diocese of Dumaguete and the local government.

The cathedral has weathered political upheaval as steadily as tropical storms. When the Philippine Revolution erupted in 1898, the Augustinian Recollect friars who had served the parish since 1855 departed, leaving secular priests in charge once more. The Philippine-American War followed, and the parish endured yet another transition of power. The Recollects returned in 1909 and reinstalled a belfry on one of the remaining watchtowers. In 1955, the church was elevated to cathedral status when the Diocese of Dumaguete was established, becoming the episcopal seat for all of the region's Catholic faithful. A monument to national hero Jose Rizal now stands in front of the cathedral, and a grotto with a praying area occupies the base of the bell tower. Through all of these transitions -- colonial, revolutionary, republican -- the stone walls and the Campanario remained, becoming the most recognized landmarks of Dumaguete and Negros Oriental.