Sousa was born a noble and participated in military expeditions in Africa, fought the Moors and commanded the nau Conceição to Portuguese India, part of the armada of Fernão de Andrade.

[1] Despite being born illegitimately, he worked for the royal court from a young age with the support of Antônio de Ataíde, his cousin and the count of Castenheira.

His objectives were to fend off French pirates and evangelize local Indians in the name of Christianity with the goal of strengthening Portugal's royal power in Brazil.

There was a decline in the spice trade and increasing threats around Brazil's borders by the surrounding Spanish colonies, which prompted Portugal to intervene.

It was supposed to bring together the twelve pre-existing settlements, though Sousa traversed the bordering areas in an effort to promote his idea of justice and to diminish what the Portuguese saw as the lawlessness and chaos of the region.

[2] He brought 1,000 colonists and soldiers with him on an expedition to Brazil, including four hundred degredados - "men banished from Portugal for some minor criminal activity.

He was successful in decreasing the hostilities waged against the colonists by native people, in part through diplomatic avenues but primarily through his use of cruel and often extreme punishment.

[1] In 1552, Sousa suggested that Rio de Janeiro might be a potential area for settlement and in 1553 he returned to Portugal to work with the King, acting as his adviser on Brazilian affairs.