He was half-brother to Don Pedro Luis de Borja (1460–88) and Girolama de Borja, children of unknown mothers.After initially entering the church and becoming a cardinal on his father's election to the Papacy, he became, after the death of his brother in 1498, the first person to resign a cardinalate.
He served as a condottiero for the King of France Louis XII around 1500 and occupied Milan and Naples during the Italian Wars.
At the same time he carved out a state for himself in Central Italy, but after his father's death he was unable to retain power for long.
According to Machiavelli this was not due to a lack of foresight but to his own illness.