In 1529 he accompanied Pizarro as a missionary, on his intended voyage of conquest to Peru. Before the battle of Caxamarca of 16 November 1532, Valverde endeavoured to obtain the Great Inca Atahuallpa's peaceful submission; later he instructed and baptized the unfortunate Inca monarch.
Following the death of Atahualpa, Pizarro saw no further obstacles to his conquest and decided to march into Cuzco on November 15, 1533, bringing Friar Vincente de Valverde along with him and his followers. By March 23, 1534, a new church was erected in Cuzco and became Friar Valverde's cathedral. Pizarro also gave him a large native commandery, which Valverde mistreated by simply using them as slaves.
Later in 1534, friar Valverde headed back to Spain to assist Pizarro's brother, Hernando Pizarro, in his negotiations at court. While in Spain, friar Valverde was also named by the empress-regent the bishop of Cuzco and Peru, since the original appointee, Fernando de Luque, had died in Panama in 1531.
By 1536 Valverde was yet again named protector of the Natives and inquisitor, and, being confirmed by the pope, he came back to Peru in the beginning of 1538, just before the execution of Diego de Almagro, which he had vainly tried to prevent.
When Emperor Charles V learned of Pizarro's victories, he named Valverde first Bishop of Cuzco, the royal city of the Peruvian kings; pope Paul III ratified his choice in a consistory held in January, 1537. The new bishop found his spiritual duties arduous, for he had already been charged with the office of Protector of the Natives. This forced him to cross the rude soldiery constantly, as the adverturers who made up the Spanish armies had no thought of justice or mercy to the Indians. He strove to settle the feud between Almagro and Pizarro and after the assassination of the latter was forced to flee from Peru. Making his way to Panama, he halted for a brief stay at the Island of Puná, near Guayaquil in Ecuador, where he was put to death by the Indians on 31 October 1541. According to some sources, the oppressed Indians revolted, captured Valverde, and poured molten gold down his throat as a punishment to greed.
By far Friar Valverde's negative and contradictory side was his mistreatment of the natives of Peru which, instead of preaching the gospel, he oppressed, enslaved, and forced to work for the church. (This was the complete opposite to what Bartolomé de Las Casas, another Spanish priest, did years later by defending the native's rights in works he published and in visits to Spain to inform King Philip II of the abuses committed against the local natives by the Conquistadors.)
Valverde was later appointed by Pizarro on the commission to apportion lands and natives to the royal officers, and the licentiate, Antonio de Game, whom Pizarro had appointed supreme judge of Cuzco. The latter charged Valverde in a letter to the emperor, dated March 10, 1539, with arbitrary acts and insisted that instead of protecting the natives, he only mistreated them and sought to confiscate their lands, and always gave the greater part to himself and his assistant. Despite the charges, on March 11, 1540, Friar Valverde officiated at the consecration of the new cathedral of Lima. He then headed back to Spain, where he presented to the emperor, by order of Pizarro, a memorial about the conquest under the title of "Relacion de la Conquista de los Reynos de Peru," in which he claimed that the natives could scarcely be considered as human beings, as they had no souls.