Soon after his accession, he was forced by Pope Pius IV to send his mother back to France due to her increasingly Calvinist beliefs.

Rudolf II, Holy Roman Emperor recognized as heir his cousin Cesare d'Este, member of a cadet branch, who continued to rule in the imperial duchies and carried on the family name.

As a result of Alfonso's death Cesare d'Este and his family were "obliged to leave the city" and the power of the government was there after turned over to the cardinal legate.

[4] Alfonso II raised the glory of Ferrara to its highest point, and was the patron of Torquato Tasso, Giovanni Battista Guarini, and Cesare Cremonini—favouring the arts and sciences, as the princes of his house had always done.

Alfonso II is the duke upon whom Robert Browning based his poem My Last Duchess, and is a major character in the Maggie O'Farrell novel The Marriage Portrait.