Pirro was the eldest son of Francesco II, third duke of Andria, and Sancia di Chiaramonte, the sister of Isabella of Clermont, the Aragonese king Ferdinand I of Naples's wife.
After her father died while fighting in the final siege of Constantinople (1453), he received from Maria Donata the fief of Venosa and other cities in the Kingdom of Naples.
However, the Aragonese obtained a decisive victory at Troia on 18 August 1462; in exchange for his loyalty, king Ferdinand gave him the fief of Ginosa and, after his father's death, named him Grand Constable of the Kingdom of Naples (1481) as well as the title of Prince of Altamura.
When he received the royal order to fight against the invasion of Abruzzo by Giovanni della Rovere, he instead occupied lands for himself at Spinazzola, Genzano and Barletta.
However, his conquest were soon lost to Ferrante of Naples and, after his hometown of Venosa had been captured, on 18 December 1486 Pirro was forced to submit to Ferdinand.