There they fought a number of battles against the natives and their leaders, mainly against the chieftain Rajah Tarik Sulayman (a name derived from Arabic طارق بن زياد "Tāriq"), Islamic settlements in Philippines were abundant before and during the Mexican-Spanish conquest.

In May 1572, Salcedo led an exploration expedition of 45 Spaniards northward and founded several Spanish settlements, including the Ilocos and the city of Vigan.

In 1574, Salcedo hurried back to Manila, when that city was threatened by a large pirate invasion led by Limahong who had sailed from the South China Sea.

Salcedo gathered 600 infantry soldiers consisting of 300 Spaniards and Mexicans, plus their allies of 300 native Filipinos to defend the settlements and drive out the 6,500 Chinese sea pirates who had laid siege on the area.

He had one older brother named Felipe de Salcedo, who was also a soldier in the Spanish army, and who accompanied him and his grandfather during their campaigns to the Philippines.

According to Philippine historical documents and a written account by Don Felipe Cepeda, Salcedo's aide,[5] who returned to Acapulco, recount that after the Spanish conquest of Luzon with Mexican and Visayan assistance, and their consequent takeover of the Pasig River delta polity of Hindu Tondo, which was the previous preeminent state in Luzon before the Brunei Sultanate established their puppet-kingdom, Islamic Manila, to supplant Tondo, Juan de Salcedo, then about 22 years old, fell in love with the 18-year-old "Dayang-dayang" (a native Filipino word for "Princess") Kandarapa, so named after the lark of the rice fields, whose song she imitated by her beautiful singing voice,[6] was said to be the niece of Rajah Lakandula, Tondo's Lakan ("Paramount ruler").

Salcedo had developed an admiration of Kandarapa's natural physical beauty, including her long black raven hair, exotic golden-brown skin features, and lavish royal lifestyle.

Among the detainees were Lakandula's son and nephew, whom López de Legazpi freed while concealing his knowledge of the rajahs of Tondo's betrayal.

De Goiti sailed into Bulakan through the twisting channels of the Pampanga, bringing Lakandula and Rajah Sulayman with them to urge the inhabitants to submit.

López de Legazpi imprisoned Lakandula after he returned to Tondo without authorization despite his eloquence in persuading the other datus (chieftains) to join the Spaniards.