Manuel da Nobrega studied humanities at Porto and Salamanca, Spain and at the University of Coimbra, where he obtained his baccalaureate in canon law and philosophy in 1541.

In 1549, he joined the naval fleet of the first Portuguese Governor-General Tomé de Sousa (1502–1579) following a request by King John III of Portugal to the Society of Jesus to start the missionary work of converting the Amerindians, who were heathen in the eyes of the Catholic Church, of building churches and religious seminars, and of educating the colonists.

He soon was fiercely engaged in the defense of the Indians, which led to serious clashes with inhabitants and authorities of the new colony, alike, including the first Governor-General and the one who succeeded him, Duarte da Costa.

To gain authority in his fight against the colonists, Nóbrega asked the King to establish an episcopacy in Brazil, which was granted on February 25, 1551.

Sensing the difficulties of converting adult Indians to Christianity, Nóbrega determined that the Jesuits' efforts should concentrate on the teaching of children, who were more pliable.

The Jesuits discovered that singing was a very effective way of winning the attention of the students, and Nóbrega was one of the pioneers in using music in education in Brazil.

There in 1553 he was joined by another group of Jesuits, who had arrived with José de Anchieta, then a young novice, who travelled with Duarte da Costa, the second Governor-General sent by the Crown.

Nóbrega determined as the new mission of the small band of missionaries to found villages (aldeamentos) on the high plateau just above the coastline to better pursue their work of catechesis and education of the Indians.

Thus, on January 25, 1554, Nóbrega and Anchieta celebrated the first mass in the new and modest Jesuit College of São Paulo dos Campos de Piratininga, in honor of Saint Paul's day of conversion to Christianity.

One of the early encounters with members of indigenous groups was when Nóbrega and his men tried to stop preparations for a cannibal feast and the natives rose against the Christians.

Although this stage in the development of the Brazilian economy was temporary, the Portuguese eventually began using African slave labor, it had long-lasting effects on the morale of the native people.

[3] Nobrega’s Diálogo sobre a Conversão do Gentio uses the point of view of two Portuguese settlers to describe the native people of Brazil.

The Tamoio and Tupiniquim tribes, who lived along the Brazilian coast from the present-day states of Espírito Santo to Paraná, were most affected.

Hard pressed, Nóbrega tried to make a peace treaty with the Confederation, sensing that all their efforts and the Portuguese colonization were in great danger.

Anchieta's command of Tupi, the language spoken by most of the Indians (of which he had compiled a vocabulary and a grammar), was extremely useful to Nóbrega, who had no such ability.

The arrival of a French invasion force in 1555, in the Guanabara Bay, Rio de Janeiro (the so-called France Antarctique episode), however, tipped the balance again since the Indians saw an opportunity to rally the Frenchmen's help to vanquish the Portuguese.

“Comparing Colonial Cultural experiences: Religious Syncretism in Brazil, Mexico and North America.” Revista Electrônica de História do Brasil.