Before his elevation to the papacy he was Vice-Chancellor of the Holy Roman Church (1227-1228), Cardinal Priest of S. Lorenzo in Lucina (September 18 1227) and governor of the March of Ancona (December 1234 until 1240). He was also elected bishop of Albenga in 1235, but resigned in 1238 without receiving episcopal consecration.
His immediate predecessor was Pope Celestine IV, who however, was pope for eighteen days only, and therefore the events of Innocent IV's pontificate practically link themselves onto those of the reign of Pope Gregory IX (1227-41).
Innocent IV was elected unanimously at the conclave in Anagni (June 25, 1243). Frederick II, who had been excommunicated by Innocent's predecessor, is said to have remarked that he had lost the friendship of a cardinal and gained the enmity of a Pope; the letter which he wrote, however, expressed in respectful terms the hope that an amicable settlement of the differences between the empire and the papacy might be reached. The negotiation which shortly afterwards began with this objective proved abortive, Frederick II being unable to make the absolute submission to the Pope's demands which was required of him. The main point of dispute was the reinstatement of the Papal rights in Lombardy.
Finding his position in Rome insecure, Innocent IV secretly withdrew in the summer of 1244 to Genoa, and thence to Lyon, where he summoned a general council which met in 1245. The council did not see the presence of delegates from the whole of Europe, the bishops present being mostly Spanish and French. Frederick II's position was defended by Taddeo of Suessa, who was however unable to prevent his deposition on July 17. The agitation caused by this act throughout Europe terminated only with Frederick II's death in December 1250, which permitted the Pope to return, first to Perugia, where he remained in 1251-1253, and afterwards to Rome.
In 1245, Innocent IV issued bulls and sent an envoy in the person of Giovanni da Pian del Carpine (accompanied by Benedict the Pole) to the "Emperor of the Tartars". The message asked the Mongol ruler to become a Christian and stop his aggression against Europe. The Khan Güyük replied in 1246 a letter written in Persian that still rests in the Vatican Library, demanding the submission of the Pope and the other rulers of Europe.
In 1245 Innocent had sent another mission, through another route, led by Ascelin of Lombardia, also bearing letters. The mission met with the Mongol ruler Baichu near the Caspian Sea in 1247. The reply of Baichu was in accordance with that of Güyük, but it was accompanied by two Mongolian envoys to the Papal seat in Lyon, Aïbeg and Serkis. They met with Innocent IV in 1248, who again appealed to the Mongols to stop their killing of Christians.
Innocent IV would also send other missions to the Mongols in 1245: the mission of André de Longjumeau, the possibly aborted mission of Laurent de Portugal, and mission of Giovanni da Pian del Carpine, which left on April 16th, 1245 and would reach the Mongol capital Karakorum.
However, Manfred had not lost his time and organized a resistance, supported by his faithful Saracen troops, setting riots against the new authority. It was on a sick bed at Naples that Innocent IV heard of Manfred's victory at Foggia against the Papal forces: the tidings are said to have precipitated his death on December 7, 1254, in Naples.
His learning gave to the world an Apparatus in quinque libros decretalium. But he also issued the papal bull Ad exstirpanda acknowledging the right of the state to punish heretics after they were convicted of heresy.