[2]   His father, who had been imprisoned for opposing encroachments on the liberties of Milan by Charles V (whom he afterwards cordially supported), removed to Modena, where his youngest son had most of his early education.

In return for important service rendered by his father, he was, on 7 April 1529, at the age of 20, nominated by Pope Clement VII to the see of Modena[3][4] as a demonstration of gratitude.

[5] His father Girolamo had been one of the commissioners who negotiated the terms of the release of the Pope from imprisonment in the Castel St. Angelo in 1527 during the Sack of Rome.

Giovanni was seven years too young to be consecrated a bishop, and in any event his appointment was disputed by the future Cardinal Ippolito II d'Este, son of the Duke of Ferrara, who claimed that the Pope had promised the See of Modena and a Cardinalate for him in a treaty of 14 November 1528.

[11] With the cardinals Pier Paolo Parisio and Reginald Pole he was deputed to open the Council of Trent (1 November 1542 – 6 July 1543), the choice of that place of meeting having been a concession to his diplomacy.

[16] But on 31 May 1557, on direct orders of Pope Paul IV, carried out by his nephew, Cardinal Carlo Carafa, Morone was imprisoned in the Castel Sant'Angelo (with others, including Bishop Egidio Foscherari), on suspicion of the Lutheran heresy.

Morone might have had his liberty, and the Suburbicarian Bishopric of Albano, but refused to leave prison unless Paul IV publicly acknowledged his innocence.

[4] Paul IV, a former Inquisitor who believed that the Inquisition was never wrong, refused to admit his error, and therefore Morone remained incarcerated until the pope's death (18 August 1559).

[21] As events turned out, Cardinal Giovanni Angelo de' Medici was elected, and took the name Pope Pius IV.

[citation needed] Upon the election of Pius IV, Morone's name was cleared publicly, and he accepted the office of Cardinal Bishop of Albano,[23] which he exchanged for that of Sabina in 1561, then Palestrina in 1562, and Porto and Santa Rufina in 1565.

Ghislieri himself was ultimately elected unanimously and took the name of Pope Pius V.[26] He became Dean of the Sacred College of Cardinals in 1570, and assumed the Bishopric of Ostia and Velletri[27] which went with the Deanship.

[28] As Cardinal Bishop of Ostia and Velletri, he was attentive to the implementation of the decrees of the Council of Trent, especially as regards the holding of regular diocesan synods.

When the festival of the Jubilee of 1575 began in Rome, Cardinal Morone presided over the ceremony of the opening of the Holy Door, through which hordes of pilgrims passed, at the Basilica of San Paolo Fuori le Mura on the Via Ostiensis.