A traveled and cultivated man, Afonso was present in 1415 when the Portuguese conquered Ceuta. When his half - brother Edward I, King of Portugal died in 1438, his son Afonso V (Afonso's nephew) was an infant and the choice for the regency was the Queen - Mother Leonor of Aragon (Afonso's sister - in - law). This choice for the regency was not popular because Leonor was Aragonese, so in a reunion of the Cortes, summoned by Afonso's half - brother John, Duke of Aveiro, another half - brother of Afonso, Pedro, was appointed as Regent of the Kingdom during the minority of his nephew Afonso V, a choice that pleased both the people and the fast growing Bourgeoisie.

However, inside the Portuguese aristocracy, especially the ones around Afonso, Count of Barcelos, Leonor of Aragon was preferred and there were doubts about Pedro's political ability. A war of influences started and a few years later Afonso managed to become young King Afonso V's favourite uncle.

In 1443, in a gesture of reconciliation, Pedro made Afonso the first Duke of Braganza and the relations between both seemed to return to normality. But, in 1445, Afonso took offence because Isabel of Coimbra, Pedro's daughter, was the choice for Afonso V's wife, and not one of her daughters. Indifferent to the intrigues, Pedro continued his regency and the country prospered under his influence. It was during this period that the first subsidies for the exploration of the Atlantic Ocean were implemented, and the organization was given to Henry the Navigator (another of Afonso's half - brothers).

On June 9, 1448, King Afonso V came of age and Pedro gave control of the country to the king. Influenced by Afonso, Count of Barcelos, and recently Duke of Braganza, Afonso V nulified all of Pedro's edicts.

The following year, under accusations that years later would prove false, Afonso V declared his uncle Pedro, Duke of Coimbra, a rebel. The situation became unsustainable and a civil war begun. It was short because on May 20, 1449, during the Battle of Alfarrobeira, near Alverca, Pedro, Duke of Coimbra died. The exact conditions of his death are debatable: some say it was in combat, other say he was assassinated by one of his own men.

After the Battle of Alfarrobeira, Afonso V gave new powers to the Duke of Braganza and nine years later when he departed to Africa, the regency was delegated to Afonso.

Afonso married twice. First, on 8 November 1401, to Beatriz Pereira de Alvim, from whom he had three children. Afonso married a second time perhaps in 1420, with his 3rd cousin, Constance of Noronha (c. 1395 - Coimbra, 26 January 1480), daughter of Alfonso, Count of Gijón and Noronha (a natural son of Henry II of Castile), and of Isabel of Portugal (a natural daughter of Fernando I of Portugal). Constance was the first Duchess of Braganza and she is buried in Guimarães. They had no issue.