The establishment of the Diocese of Manila marked a pivotal moment in the religious landscape of the Philippines, reflecting the expanding reach of the Catholic Church during the Spanish colonial era. Pope Gregory XIII issued the papal bull, which formally created the diocese, emphasizing the importance of spiritual governance in the newly acquired territories. Domingo de Salazar, a Dominican friar, was chosen as the first bishop due to his previous experiences and commitment to missionary efforts in the region.

Manila, the capital of the Philippines, became a focal point for the Catholic Church in Asia and played a critical role in the evangelization of the local population. The appointment of Salazar came during a time when the Spanish were eager to consolidate their power and influence, both politically and religiously, in the archipelago. The diocese was tasked with overseeing the spiritual welfare of the faithful and managing the affairs of the Church in this emerging colonial territory.

The establishment of the diocese had profound implications. It facilitated the construction of churches, schools, and other institutions that would spread education and literacy among Filipinos. The framework set in place by Salazar would not only impact the religious dominion but also the cultural and social structures of Manila and its surroundings. Salazar's leadership marked a transition toward a more organized and systemic approach to mission work, aligning with Spanish colonial policies.