He served the Spanish Crown with such efficiency and loyalty that King Philip II rewarded him in 1575 with the title of Marqués de Villamanrique.
At this time Manrique de Zúñiga had lived for several years in Seville, where he had gained indirect experience with the Indies.
Manrique de Zúñiga began his administration by completing the regulations introduced by the previous viceroy governing the sale of wine in the colony, and the location of taverns.
On August 6, 1587, the port of Huatulco (Oaxaca) fell to English corsair Thomas Cavendish, and on September 3, 1587, he sacked Navidad (Jalisco).
Each Manila galleon was loaded with a year's worth of treasure from the Philippines en route to Acapulco for ultimate delivery to Spain.
Manrique de Zúñiga's response included the establishment of a militia of volunteers to defend Pacific ports and the arming of Spanish ships to fight the pirates at sea.
Manrique took important steps toward ending the long-running Chichimeca War on New Spain's northern frontiers which threatened communications with silver mines near the city of Zacatecas.
He opened negotiations with Chichimeca leaders and promised them food, clothing, land, priests, and tools to encourage them through “gentle persuasion” to settle down.