Facchinetti was born in Crodo, in the diocese of Novara, northern Italy. He was a lawyer, a graduate in 1544 of the University of Bologna, which was pre-eminent in jurisprudence, and became secretary to Cardinal Nicolò Ardinghelli before entering the service of Cardinal Alessandro Farnese, brother of the Duke of Parma and nephew of Pope Paul III (1534-1549), one of the great patrons of the time. The Cardinal, who was archbishop of Avignon, sent Facchinetti there as his ecclesiastical representative and subsequently recalled him to the management of his affairs at Parma, where he was acting governor of the city, from 1556 to 1558. In 1560, Facchinetti was named Bishop of Nicastro, in Calabria, and in 1562 was present at the Council of Trent. Pope Pius V (1566-1572) sent him as papal nuncio to Venice in 1566 to further the papal alliance with Spain and Venice against the Turks, which ultimately resulted in the victory of Lepanto in 1571. Relinquishing his see to pursue his career in Rome, he was named titular Latin Patriarch of Jerusalem in 1572.
During the reign of the sickly Gregory XIV, who suffered from bouts of malaria, the burden of the papal administration rested on his shoulders. Even before Gregory XIV breathed his last, Spanish and anti-Spanish factions were electioneering for the next Pope. Philip II of Spain's (1556-1598) high-handed interference at the previous conclave was not forgotten: he had barred all but seven cardinals. This time the Spanish party in the College of Cardinals did not go so far, but they still controlled a majority, and after a quick conclave they raised Facchinetti to the papal chair as Pope Innocent IX. Mindful of the origin of his success, Innocent IX supported, during his two months' pontificate, the cause of Philip II and the Catholic League against Henry IV of France (1589-1610) in the civil Wars of Religion (1562-1598), where a papal army was in the field. Death, however, did not permit the realization of Innocent IX's schemes.
His great-nephew Cardinal Giovanni Antonio Facchinetti de Nuce, juniore, was one of two Cardinals appointed during the weeks of Innocent IX's pontificate. A later member of the Cardinalate was his great-grand-nephew Cesare Facchinetti (made a Cardinal in 1643).