Bernacchi was born in Bologna and, having been engaged at the court of Johann Wilhelm, the Elector Palatine in 1701, began his operatic career in Genoa in 1703.
His appointment in 1714 as virtuoso to Prince Antonio Farnese led to widespread recognition throughout Europe, and he performed in operas by various famous composers of the day, including Johann Adolph Hasse, Leonardo Vinci, and Alessandro Scarlatti (Rome 1721).
Despite his fine European reputation, Bernacchi's success in England was mixed: though Charles Burney praised his intelligence as a singer, English audiences preferred Senesino.
He was much lamented by his fellow citizens, while Farinelli, a friend as well as a rival and sometime pupil, arranged an elaborate memorial service in his honour.
However, others accused him of sacrificing expression to virtuosity by adopting an excessively instrumental style; in exasperation, his former teacher Pistocchi lamented: "Tristo a me, io t'ho insegnato a cantare, e tu voui suonare!"