Following his sudden heart attack, Pope Pius XIII lies in a coma while his followers fervently pray for a miraculous recovery. As the threat of terrorism and the potential risks of Pius's idolatry loom, Secretary of State Cardinal Voiello is pressured to bring a new pope to power and, with the conclave at a deadlock, makes a hasty move that throws the Church into even greater chaos.
As rumors swirl about the Church's role in a sudden death, Voiello, Gutierrez, Assente, Aguirre and Sofia travel to the UK to the grand estate of Sir John Brannox, hoping to convince him to return with them to the Vatican and accept the holiest of roles. An alluring but sensitive man who carries with him an unshakeable family tragedy, Brannox is harder to sway than expected, but a determined Voiello presses ahead. Meanwhile, Ester shares her son's story with the press to makes ends meet.
Still considering the offer of Supreme Pontiff, Brannox reflects on his past, while Voiello makes clear his commitment to his mission's success. After being elected pope and taking the name "John Paul III," Brannox preaches the importance of family, truth and love in his first public homily and to the cardinals. Ester bonds with Fabiano, a widower and new member of the parish, who offers an unusual solution to her money woes. The Abbess of St. Therese and an anguished Sister Lisette are disheartened when their financial pleas fall on deaf ears.
Following an audience with Marilyn Manson, Brannox decides to pay a visit to Pius XIII and is confronted with the intensity of his predecessor's followers. Later, Brannox appoints Cardinal Spalletta, with whom he shares a past, to a new role. Voiello prepares for a long war with the defiant Sister Lisette after the nuns go on strike. The Church faces the prospect of bankruptcy as the Italian government looks to make changes. Gutierrez has a clandestine meeting, which he later confesses to the pontiff. An angry Fabiano questions Ester's commitment to her faith.
A brutal act of terrorism in France leads to an unconventional response from the pope that strikes a chord with the public. Feeling disconnected from her husband, Sofia reaches out to Brannox, who shares more of his personal history. Pius XIII's followers flock to Venice when there's a sudden change in his condition.
A confrontation with Spalletta leads Brannox to deliver some unwelcome news to Voiello. Sofia learns what her husband has been keeping from her. Voiello ties up loose ends. Ester expands her business and takes drastic action when she is met with opposition. Brannox agrees to a live televised interview that asks him to delve into his past.
In Venice, a papal doctor and his wife struggle to care for their sick son and witness a miracle. Pius XIII's devotees grow resigned and change course. An attack on Vatican soil shakes Brannox to his core and prompts him to admit a hard truth to Gutierrez. Sofia comes to Voiello for advice on how to handle the pope.
Sofia sets out to bring an ashamed Brannox back to the Vatican from the Dolomites, where the two share an intimate moment. Warned by Bauer of the Church's demise unless immediate action is taken, Voiello is called upon to make things right and, later, mourns a tragic loss. The nuns appeal to an unaccommodating Assente.
John Paul III addresses his followers with a message of love that resonates. A historic meeting of the minds occurs after six children and their teacher are taken hostage on the island of Ventotene. As the Church prepares for battle, Voiello receives a visit from a man close to the caliph and a rescue mission has an unexpected conclusion.