While Larry Belardo begins his pontificate as Pius XIII, he calls on Sister Mary, his childhood guardian for help, and begins to familiarize himself with the Vatican.

Lenny shocks the world with his first address, in which he demands Catholics worldwide devote themselves body and soul to God no matter the consequences. Sister Mary and Cardinal Voiello struggle to control Lenny, who admits that his conservative religious views were caused due to his parents abandoning him to an Italian orphanage to continue a hedonistic lifestyle.

In the wake of Pius's homily, multiple factions within the Vatican bond together, trying to seek anything they can find on their new pope. Lenny plans to bring forth a new resurgence of conservative Christianity as his former mentor, Cardinal Spencer, struggles with Cardinal Voiello over their inability to control the new Pope. Lenny forces Voiello to reveal that liberal forces in the College of Cardinals blocked Spencer's election as Pope, resulting in an agreement between the two men to use Lenny as a puppet to control the Papacy. When Lenny threatens to excommunicate Voiello, the liberal cardinal is forced to swear loyalty to him. Later, a chance encounter with Esther, the wife of a Pontifical Swiss Guard, leads to Lenny having a seizure in her presence. Lenny agrees to a press conference, making his counselor Sister Mary read a short statement.

Cardinal Voiello urges the young Pope Pius XIII to finally deal with the abuse scandal surrounding American Cardinal Kurtwell. The Pope shocks Voiello by requesting to remove all homosexuals from the Catholic Church without regard to the person. Lenny arranges for a nun's sister to be brought to the Vatican for burial, then berates her at the funeral for crying. Lenny denies a promotion for Spencer and severs ties with him, as punishment for his attempt to use him. Voiello arranges for Esther to work as an assistant to the young Pope in hopes that a sex scandal might ensue that he can use as leverage. After, Lenny makes a homophobic comment about an aide to the female chancellor of Greenland, who he flirts with during a meeting.

Voiello catches Pius in a compromising situation but hesitates to use the evidence against the Young Pope. More is revealed about Lenny's troubled past as he and Dussolier reconnect while running away from Sister Mary again. Gutierrez is assigned to an uncomfortable appointment in America. Upon the return of a famous papal headdress to the Vatican, Pius is finally prepared to deliver his opaque and rigid address to the Cardinals.

Nine months into Lenny's papacy, he gives his first audience to the Italian prime minister. Dussolier carries out a controversial edict.

Pius's opposition consolidates against him as his plan for a conservative revolution in the church continues to alienate the public. Sister Mary commits herself to deception. In the wake of a tragedy, Dussollier blames himself and decides to return to his mission in Honduras.

Pius struggles with emotional fallout from Dussolier's death. Admist feminist protests, author Elmore Coen (Andre Gregory) visits Pius for a conversation about sex. Spencer offers Pius spiritual guidance for handling his increasing guilt. Hoping to find clarity in his Papacy, Pius follows Sophia's suggestion to visit an African mission where he discovers moral ambiguity. Meanwhile, Pius's relation with the public grows more contentious as reporters begin digging into his past.

Gutierrez grapples with his alcoholism while investigating the crimes of Archbishop Kurtwell. As Spencer's condition worsens, Lenny opens up about the mysteries of his past. Meanwhile, Kurtwell attempts to retaliate against Pius by leaking unsent love letters to the press.

The Young Pope makes travel plans to Guatemala, to change them last minute, to "find God" in Venice, Everything changes and the finale remains open.