The eruption of the Protestant Reformation in the first decades of the sixteenth century brought forth a Roman Catholic response, the Counter-Reformation, a determined campaign to strengthen the Roman Catholic Church and restore religious unity to Europe. One of Rome's key instruments to purify doctrine and root out heresy was the Inquisition. The Counter-Reformation soon reached Portugal and Joao III was granted permission to establish the Court of Inquisition in 1536. The court did not began its work until 1539 when the first inquisitor general was replaced by a religious zealot, the archbishop of Évora, who stood for public confession and immediate execution. As elsewhere, the Inquisition in Portugal dealt with all forms of heresy, corruption, and disbelief, but its main victims were the so-called New Christians, Jews who had converted to Christianity after Manuel I had ordered in 1497 the expulsion from Portugal of all Jews who refused to accept the Christian faith. Many Portuguese believed that the New Christians secretly practiced Judaism at home and the Inquisition was used to stop such an "abomination." Courts of the Inquisition functioned in larger settlements around Portugal. The first auto-da-fé, or public burning of a heretic, took place in 1540 in Lisbon. In the next 150 years, an estimated 1,400 people perished in this manner in Portugal.

Another of Rome's strongest weapons in the CounterReformation was the Society of Jesus, a religious order founded by Ignatius de Loyola in 1539. The order was dedicated to furthering the cause of Catholicism and propagating its teachings in missions among nonbelievers. In 1540 three of Loyola's followers, Simão Rodrigues, who was Portuguese Paulo Camerte, who was Italian and Francisco Xavier, who was Spanish arrived in Portugal. Simão Rodrigues became the tutor of the king's son and later founded Jesuit schools at Coimbra and Évora. By 1555 the Jesuits had control of all secondary education in the realm and by 1558 had established a university in Évora.

João III invited the Jesuits to carry out their apostolic mission in the lands of Portugal's overseas empire. Francisco Xavier left Portugal in 1541 for India as a result of the king's request. He arrived in Goa in 1542 and immediately began prosletyizing among the indigenous inhabitants, converting many thousands. From Goa he went to Cochin and Ceylon in 1545 he traveled to Malacca, and in 1549, to Japan, where he stayed for two years. After returning to Goa, in 1552 he went to China, where he died.

Evangelization began in Brazil in 1549 with the arrival of six Jesuits led by Father Manuel de Nóbrega, who accompanied Tomé de Sousa, the first governor general. They built a church at São Salvador da Baía, as well as schools at Rio de Janeiro and São Paulo. They evangelized northern and southern Brazil. In the south, Father José Anchieta opened a school for Indians and authored the first grammar in a native language, Tupí-Guaraní. The Jesuits built churches, schools, and seminaries. They settled the indigenous inhabitants in villages and defended156 ed them against attempts to enslave them.

Data as of January 1993