Isabella was the daughter of Pirro del Balzo, duke of Andria and Prince of Altamura,[1] and Maria Donata Orsini of Venosa.
In the marriage contract, she was declared to be the heir of her parents' territories, despite the fact that she was not their eldest child, which meant that her fiefs were to be inherited by her issue and then further in to the Neapolitan royal house.
After the wedding she therefore remained in the Castle of Andria in Apulia, rather than joining the royal court of Naples.
In 1495, during the war against France, Isabella was ordered by Frederick to seize control over the Castle of Bari and repair its fortifications, which she did.
Isabella initially escaped to Ischia with her children in August 1501, but later followed Frederick to France, where he was given an allowance.
Isabella found a refuge for herself and younger children in the Duchy of Ferrara under the protection of Frederick's nephew Alfonso d'Este, and lived there until her death, never remarrying.
Isabella was portrayed by Baldassare Castiglione as an ideal example of a woman and a queen to have bravely endured her many strikes by faith.