The founding of St. Dominic's traces back to three Spanish Dominican priests who arrived in Macau in 1587, having traveled from Acapulco, Mexico — a reminder of how thoroughly the Iberian empires of the sixteenth century had connected the Pacific into a single commercial and religious network. Spain and Portugal were at that time unified under the Iberian Union, which meant Spanish religious orders could operate across Portuguese territories. The church those priests established was finished in 1587, though the current structure dates from the early seventeenth century due to subsequent renovations and reconstruction. Its Baroque style — the yellow facade, the tiered white pilasters, the bell tower visible from Senado Square's northern end — reflects the exuberance of Counter-Reformation church design interpreted through a Macanese lens. Chinese-style roof tiles and doors made of teak mark the building as a product of its particular place, not a straight import from Lisbon or Seville.

In 1644, the Iberian Union ended when Portugal reasserted its independence from Spain. In Macau, the political rupture produced immediate violence. A Spanish military officer — loyal to the Spanish crown and unwilling to accept Macau's allegiance to the newly independent Portugal — entered St. Dominic's Church to seek refuge from an angry mob. He did not find it. He was killed at the foot of the altar while mass was being celebrated, a moment of exceptional brutality in a sacred space that nonetheless tells a recognizable story: empire is political, and politics inside empire can be vicious. The church that witnessed the murder continued standing, continued holding services. The incident passed into history as a footnote to a dynastic conflict most of the world has forgotten, preserved mainly because it happened in a building that survived.

The liberal revolution in Portugal brought monastic orders under increasing pressure throughout the empire. In 1834, those orders were dissolved and their properties expropriated. St. Dominic's Church closed. The government took possession of a Baroque church on a prominent square and converted it into barracks, then a stable, then an office for public works — a sequence of uses that was simultaneously practical and desecrating. It stayed in secular hands for decades. The eventual return of the building to ecclesiastical use, and its subsequent renovation in 1997, did not erase those years; they are part of what the building is. By the time UNESCO inscribed it as part of the Historic Centre of Macau in 2005, St. Dominic's had earned its World Heritage status not through pristine preservation but through improbable survival.

Visitors entering St. Dominic's today encounter a high altar centered on a statue of the Madonna and Child, flanked by carved wood and ivory statues of saints — a rich devotional interior that demonstrates how thoroughly Baroque Catholicism had absorbed artistic traditions from across its global network. The teak doors and Chinese roof tiles visible on the exterior continue inside as a material argument about Macanese identity: neither purely European nor purely Chinese, but something made in the encounter between them. A museum added during the 1997 renovation, the Treasure of Sacred Art, occupies the upper floors and displays religious objects accumulated over four centuries of church history. The collection is modest by European standards and remarkable by any measure of what survived the building's secular interlude as a military barracks. That it exists at all is its own form of testimony.