Alfonso, son of Ercole II d'Este and Renata di Francia, was always linked to his mother's family and, from an early age, lived for long periods at the French court, host of his uncle, Henry II. When, on October 3, 1559, his father Ercole II died, he was in France. Alfonso immediately returned to Ferrara and chosed a path that led him to embark, to arrive in Livorno and then across the Garfagnana, the Apennines, go through Modena and finally get to Ferrara, where he officially took power.
One of the first decisions he took as duke was to pardon Giulio d'Este, who had been held prisoner for 53 years in the Este castle. A second important act, at the request of Pope Pius IV who did not like his Calvinist positions, was the removal of his mother, Renata di Francia from the Este court, in 1560.
At the time of the investiture he was married to Lucrezia de 'Medici, who died in 1561 leaving him without children. Later he decided to marry Barbara of Austria, but the weddings were delayed due to the death of her father, Ferdinand I of Hapsburg. When they were finally celebrated, in 1565, Alfonso had now tightened a strong alliance with Austria and the following year he went with his forces in support of Emperor Maximilian II of Habsburg, engaged in the Austro-Turkish war.
At the death of Barbara, in 1572, still without a lineage, he sought a new wife, and the choice fell on Margherita Gonzaga, 31 years younger and belonging to a family traditionally close to the Este. Once again Alfonso had no heirs, and it was therefore clear that the problem depended on him, and not on his wives.
The duke managed power in a period of substantial static equilibrium, in Italy, waiting for opportunities for his State that did not arrive, now sorrounded between the Hapsburg Empire and Spanish dominion. At his service, as had already happened with his predecessor Ercole II, he worked Annibale Borgognoni, one of the most famous masters of the artillery of 1500.
With him the court of Ferrara reached levels never reached before splendor and magnificence, and the houses of the Este reached their maximum grandeur. For example, on his assignment, the Chapel known as Renata di Francia was designed and built by the architect Alessandro Balbi in the Estense Castle. The large expenses incurred for these works and for the numerous celebrations of that period produced problems for the public coffers, leading often to financial difficulties and tax raisings.
He hosted poets and artists thus continuing in the Este tradition. He was protector of Torquato Tasso and continued in the policy of military strengthening, even if the international political evolution did not offer many occasions to demonstrate the always fearful power of the Este artillery. To Alfonso II some historians attribute the desire to have a large open area constructed which corresponds to the Cortile Theater about the current parking in Contrada di Borgoricco. According to others, the theater was to be built only in 1610, according to a project by architect Giovan Battista Aleotti.
During the duchy of Alfonso II Ferrara was hit by a seismic swarm with peaks in 1561, in 1570 and in 1591. In this regard it is interesting to remember the presence in Ferrara in those years of Pirro Ligorio, who was Michelangelo's successor in the San Pietro, in Rome and who, having moved to the Estense capital and witnessing the devastating effects of the earthquake on the buildings, had the intuition of the first house built with anti-seismic criteria.
A papal bull issued on May 3, 1567 by Pope Pius V (Prohibitio alienandi et infeudandi civitates et loca Sanctae Romanae Ecclesiae) officially called the duchy on the conditions that would have been missing, in the absence of legitimate heirs, to the permanence of the Este in power .
Alfonso then, still alive, first tried to have legitimate heirs, and, in the absence of these, he designated to his succession his cousin Cesare (son of Alfonso, brother of his father Ercole II d'Este), and the act was recognized by the Empire, but not from the Church, as uncle Alfonso was the natural son of the predecessor Duke Alfonso I d'Este and Laura Dianti. Then, at his death, Pope Clement VIII re-appropriated the city, an ancient papal fiefdom, bringing Ferrara back under the direct jurisdiction of the Papal State. This transfer of powers is called devolution.
After his death he was buried in Ferrara in the Corpus Domini Monastery.