The son of Orso Orsini and Lucrezia Conti, Jacopo succeeded his father as lord of Monterotondo.
In 1431, he received the castle of Calvi on behalf of the Papal State.
In 1433, on the orders of Pope Eugene IV, he sent a hundred troops to Orte to defend it against Niccolò Fortebraccio.
In 1480, he brought Lorenzo de' Medici's congratulations to the recently elected Pope Sixtus IV.
In 1482, he served the Republic of Venice as a condottiero (mercenary captain) during the War of Ferrara.