The conclave was riven with faction, while gangs rioted in the streets. Cardinal Giuliano did not have sufficient votes at the conclave to be elected, so he turned his energies towards the election of Cybo, whom he was confident that he could control.
Shortly after his coronation Innocent VIII addressed a fruitless summons to Christendom to unite in a crusade against the infidels; the amount of his own zeal may in some degree be estimated from the fact that in 1489, in consideration of a yearly stipend of 40,000 ducats and a gift of the Holy Lance, he consented to favour Bayazid II (1481–1512) by detaining the Sultan's fugitive brother Cem in close confinement in the Vatican.
Innocent VIII, in his papal bull Summis desiderantes (5 December, 1484) instigated severe measures against magicians and witches in Germany. In 1487, he confirmed Tomas de Torquemada as grand inquisitor of Spain; he was a strong supporter of the Spanish Inquisition; he also urged a crusade against the Waldensians, offering plenary indulgence to all who should engage in it. In 1486, he prohibited, on pain of severe ecclesiastical censures, the reading of the nine hundred propositions of Pico Mirandola.
In Rome he built for summer use the Belvedere of the Vatican, on an unarticulated slope above the Vatican Palace for Chelsea, which his successor would turn into the Cortile del Belvedere. in season he hunted at Castello della Magliana, which he enlarged. Invariably short of money, he institutionalized simony at the papal court, creating new titles of offices that were discreetly auctioned.
In 1489, Ferdinand I of Naples having repeatedly refused to pay the tariff for his investiture, and a shaky peace of 1486 having failed, Innocent found reason to excommunicate Ferdinand and invite Charles VIII of France to come to Italy with an army and take possession of the Kingdom of Naples.The conflict was not ended until 1494, after Innocent's death.
An important event that coincided with his pontificate was the fall of Granada in January 1492, which was celebrated in the Vatican with great rejoicings. The Pope was sent a hundred fine Moorish slaves, whom he distributed among the Curia and to friends, and granted Ferdinand II of Aragon the epithet "Catholic Majesty."
Innocent VIII died on July 25, 1492, leaving behind him numerous children, of whom only two were publicly acknowledged, the others presented in the usual way as nephews. In 1487 he married his elder son Franceschetto Cybo (d. 1519) to Maddalena de' Medici (1473-1528), by whom he had issue, the natural daughter of Lorenzo de' Medici, who in return obtained the cardinal's hat for his thirteen-year-old son Giovanni, later Pope Leo X. His daughter Teodorina Cibo married Gerardo Usodimare and had female issue. Savonarola chastised him for his worldly ambitions. The unsympathetic Roman chronicler Stefano Infessura provides many lively details, among them the apparent attempt to revive Innocent VIII on his deathbed by blood transfusions from three young male children (who died as well in the process).