He had for his immediate predecessor Celestine IV, who however, was pope for eighteen days only, and therefore the events of Innocent's pontificate practically link themselves on to those of the reign of Gregory IX. It was on occasion of Innocent's election (June 28, 1243) that Frederick II 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 being unable to make the absolute submission to the pope's demands which was required of him.
Finding his position in Rome insecure, Innocent secretly withdrew in the summer of 1244 to Genoa, and thence to Lyons, where he summoned a general council which met in 1245 and deposed Frederick. The agitation caused by this act throughout Europe terminated only with Frederick's death in 1250, which permitted the pope to return, first to Perugia, and afterwards in 1253 to Rome.
The remainder of his life was largely directed to schemes for compassing the overthrow of Manfred, the natural son of Frederick II, whom the towns and the nobility had for the most part received as his father's successor. It was on a sick bed at Naples that Innocent heard of Manfred's victory at Foggia, and the tidings are said to have precipitated his death on December 7, 1254.
His learning gave to the world an Apparatus in quinque libros decretalium, which is highly spoken of; but apart from that Innocent IV is considered a small-minded man, whose avarice, cowardice, cunning, and vindictiveness suggests a striking contrast with Innocent III, whose character and career, if his selection of a name may be taken as an indication, he seems to have admired and sought to follow. He was succeeded by Alexander IV, and was the uncle of Adrian V.