Ferdinand Magellan set out from Spain in 1519 on the first voyage to circumnavigate the globe with five ships and a complement of 264 screw. Three years later in 1522, only the one ship, the Victoria, returned to Spain with 18 men.

Magellan was welcomed by two Rajas, Kolambu and Siagu. He named the island the Archipelago of San Lazaro, erected a cross and claimed the lands for Spain. The friendly Rajas took Magellan to Cebu to meet Raja Humabon. Humabon and 800 Cebuanos were baptized as Christians. Magellan agreed to help Raja Humabon put down Lapu-Lapu, a rebellious datu on the nearby island of Mactan. In a battle between Spanish soldiers and Lapu-Lapu's warriors, Magellan was killed on April 27, 1521. disputes over women caused relations between Raja Humabon and the remaining Spaniards to deteriorate. The Cebuanos killed 27 Spaniards, deciding to resume their explorations, departed Cebu.

Four more expeditions followed between 1525 and 1542. The commander of the fourth expedition, Ruy Lopez de Villalobos, named the island after Philip, heir to Spanish throne (r. Philip II 1556-1598).

The Philippines was not formally organized as a Spanish colony until 1565 when Philip II appointed Miguel Lopez de Legazpi the first Governor-General. Legazpi selected Manila for the capital of the colony in 1571 because of its fine natural harbor and the rich lands surrounding the city that could supply it with produce.