He had already become famous for zeal and eloquence, and was the intimate friend of the Spaniard Juan de Valdes, of Bembo, Vittoria Colonna, Pietro Martire, Carnesecchi, and others destined to incur the suspicion of heresy, either from the moderation of their characters or from the evangelical tincture of their theology.
In 1538 he was elected vicar-general of his order; in 1539, urged by Pietro Bembo, he visited Venice and delivered a remarkable course of sermons, showing a decided tendency to the doctrine of justification by faith, which appears still more evidently in his dialogues published the same year. He was suspected and denounced, but nothing ensued until the establishment of the Inquisition in Rome in June 1542, at the instigation of the austere zealot Carafa.
Ochino almost immediately received a citation to Rome, and set out to obey it about the middle of August. According to his own statement, he was deterred from presenting himself at Rome by the warnings of Cardinal Contarini, whom he found at Bologna, dying of poison administered by the reactionary party. He turned aside to Florence, and after some hesitation escaped across the Alps to Geneva. He was cordially received by Calvin, and published within two years several volumes of Prediche, controversial tracts rather than sermons, explaining and vindicating his change of religion. He also addressed replies to Vittoria Colonna, Tolomei, and other Italian sympathizers who were reluctant to go to the same length as himself.
His own breach with the Roman Catholic Church was decisive and irreparable, and illustrated the justice of Luther's description of justification by faith alone as the articulus stantis vel cadentis ecclesiae, the vital point whose acceptance or rejection drew everything else along with it. In 1545 he became minister of the Italian Protestant congregation at Augsburg, which he was compelled to forsake when, in January 1547, the city was occupied by the imperial forces. He found an asylum in England, where he was made a prebendary of Canterbury, received a pension from King Edward VI's privy purse, and composed his capital work, the Tragoedie or Dialoge of the unjuste usurped primacie of the Bishop of Rome, etc. This remarkable performance, originally written in Latin, is extant only in the 1549 translation of Bishop John Ponet, a splendid specimen of nervous English.
The conception is highly dramatic; the form is that of a series of dialogues. Lucifer, enraged at the spread of Jesus' kingdom, convokes the fiends in council, and resolves to set up the pope as antichrist. The state, represented by the emperor Phocas, is persuaded to connive at the pope's assumption of spiritual authority; the other churches are intimidated into acquiescence; Lucifer's projects seem fully accomplished, when Heaven raises up Henry VIII of England and his son for their overthrow. The conception bears a remarkable resemblance to that of Paradise Lost; and it is nearly certain that Milton, whose sympathies with the Italian Reformation were so strong, must have been acquainted with it. Several of Ochino's Prediche were also translated into English by a lady, Anna Cooke, afterwards wife of Sir Nicholas Bacon; and he published numerous controversial treatises on the Continent.
In 1553 the accession of Mary I drove Ochino from England. He became pastor of the Italian congregation at Zürich, composed principally of refugees from Locarno, and continued to write books which, repeating the history of his early works, gave increasing evidence of his alienation from the strict orthodoxy around him. The most important of these was the Labyrinth, a discussion of the freedom of the will, covertly assailing the Calvinistic doctrine of predestination.
In 1563 the long-gathering storm of obloquy burst upon the occasion of the publication of his Thirty Dialogues, in one of which his adversaries maintained that he had justified polygamy under colour of a pretended refutation. His dialogues on divorce and the Trinity were also obnoxious. No explanation was allowed. Ochino was banished from Zürich, and, after being refused a shelter by other Protestant cities, directed his steps towards Poland, at that time the most tolerant state in Europe. He had not resided there long when an edict appeared (August 8, 1564) banishing all foreign dissidents. Fleeing the country, he encountered the plague at Pińczów; three of his four children were carried off; and he himself, worn out by misfortune, expired in solitude and obscurity at Slavkov in Moravia, about the end of 1564.
His reputation among Protestants was at the time so bad that he was charged with the authorship of the treatise De tribus Impostoribus, as well as with having carried his alleged approval of polygamy into practice.
It was reserved for his biographer Karl Benrath to justify him, and to represent him as a fervent evangelist and at the same time as a speculative thinker with a passion for free inquiry, always learning and unlearning and arguing out difficult questions with himself in his dialogues, frequently without attaining to any absolute conviction. The general tendency of his mind, nevertheless, was counter to tradition, and he is remarkable as resuming in his individual history all the phases of Protestant theology from Luther to Socinus. He is especially interesting to Englishmen for his residence in England, and the probable influence of more than one of his writings upon Milton.