Because he was the fourth son, after the infantes John, Luís, and Ferdinand, he was assigned by his father to religious life, and he accumulated numerous ecclesiastical benefits even though he did not have the canonical age required to exercise these dignities.

After the embassy led by Tristão da Cunha which Manuel I sent to Pope Leo X in 1514, and which left the Roman Curia very impressed, the Portuguese king again proposed his son for the cardinalship.

The pope finally agreed to the request of the Portuguese monarch and created a cardinal Alfonso on July 1, 1517, with the title of cardinal-deacon of Santa Lucia in Septisolio.

He appointed as his vicar in the Lisbon archdiocese the dean of the cathedral, Fernão Gonçalves, who conducted pastoral affairs during his minority.

He established his habitual residence in the city of Évora, just as his younger brother, also dedicated to the ecclesiastical career, the cardinal-infante Dom Henrique, would later do.