Ferdinand Magellan's arrival in Cebu represents the first attempt by Spain to convert natives to Christianity. According to a description of events, Magellan met with Raja Humabon of Cebu, who had an ill grandson whom the explorer, or one of his men, was able to help cure. Out of gratitude, Humabon and his chief consort allowed themselves to be christened "Carlos" and "Juana", with some 800 of his subjects also being baptised. Later, Lapulapu, the monarch of neighbouring Mactan Island had his men killed Magellan and routed the ill-fated Spanish expedition.

In 1564, Luís de Velasco, the Viceroy of New Spain, sent the Basque explorer Miguel López de Legazpi to the Philippines. Legazpi's expedition, which included the Augustinian friar and circumnavigator Andrés de Urdaneta, erected what is now Cebu City under the patronage of the Holy Child, and later conquered the Kingdom of Maynila in 1571 and the neighbouring Kingdom of Tondo in 1589. The colonisers then proceeded to proselytise as they explored and subjugated the remaining parts of what is now the Philippines until 1898, with the exception of parts of Mindanao, which had been Muslim since at latest the 10th century CE, and the Cordilleras, where numerous mountain tribes maintained their ancient beliefs as they resisted Western colonisation until the arrival of the United States in the early 20th century.