The film immerses viewers in the enigmatic and highly political process of selecting a new Pope following the sudden death of the previous pontiff from a heart attack. The narrative unfolds within the seclusion of the Vatican's College of Cardinals, under the direction of Cardinal-Dean Thomas Lawrence. This setting serves as the backdrop for a compelling exploration of power, faith, and morality as Lawrence unexpectedly encounters Archbishop Benitez of Kabul, who arrives with a bombshell revelation: the late pope clandestinely consecrated him as a cardinal.

This stunning revelation sets the stage for the intense papal conclave, where four prominent candidates vie for the papacy. Each of these cardinals embodies distinct ideological factions within the Church. Cardinal Bellini represents a liberal continuity with the policies of the deceased pope, advocating for a progressive direction. On the opposite spectrum stands Cardinal Tedesco, a reactionary figure with a vision to dismantle the progressive policies of the Second Vatican Council and embodying unsettling racist attitudes. Cardinal Adeyemi, with his economically progressive yet socially conservative stance, commands respect, while Cardinal Tremblay, a traditionalist, occupies the mainstream conservative position. The interplay of these characters gives rise to a complex political chess game, with each candidate maneuvering to secure the position of ultimate authority.

Beneath the surface, however, darker machinations are at work. Rumors suggest that Tremblay and Adeyemi played a role in overburdening the former pope, contributing to his demise. Amidst this contentious environment, Bellini and Lawrence emerge as de facto leaders of the Church's liberal wing, although both publicly declare their reluctance to shoulder the papal mantle. Bellini's feigned disinterest aims to engender respect among the electorate, while Lawrence wrestles with a deeply personal crisis of faith that previously saw him attempt to step down from his influential position. Notably, Lawrence, despite his reservations, casts his vote for Bellini, though Bellini suspects him of withholding full support in a move that seeds further intrigue.

The conclave itself is marred by internal conflicts and political grandstanding. Lawrence takes a pivotal role when he delivers a speech that champions diversity, interpreted by some as a disguised campaign speech. As the conclave progresses, Lawrence clandestinely initiates an independent investigation into the leading candidates, gathering intelligence under the guise of safeguarding the Church. This produces a startling disclosure: the late pope had dismissed Tremblay on the day of his death, a fact Tremblay vehemently denies, even as conflicting testimonies raise doubts.

The first vote proves inconclusive, with no candidate mustering the requisite two-thirds majority for election, leaving Adeyemi with a slight advantage. Tension mounts as five cardinals cast unexpected votes for Lawrence, provoking outrage from Bellini. This fracture in the liberal camp allows Adeyemi to gain traction, prompting Bellini, despite his disdain for Adeyemi's homophobia, to forge an uneasy alliance with Tremblay in exchange for a promise of bureaucratic favor.

The drama intensifies when a nun confronts Adeyemi in a crowded cafeteria, revealing the existence of a child conceived during a clandestine liaison between them. This revelation, a ticking time bomb, reaches Lawrence, who keeps Adeyemi's secret while a murmur campaign subtly erodes Adeyemi's momentum. Meanwhile, a savvy manipulation orchestrated by Tremblay, who arranged the nun's reassignment to the Vatican, emerges. Lawrence attempts to wield this discovery to oust Tremblay, only for Tremblay to proudly reveal his hand in the scandal and accuse Lawrence of exploiting the conclave for personal gain.

As Lawrence unravels departmental documents in the late pope's quarters that expose Tremblay's vote-buying schemes, the fragile alliance within the conclave collapses. Bellini, initially complicit, reevaluates his allegiance, swaying his support to Lawrence. Emboldened by sleuthing with Sister Agnes, Lawrence and Agnes strategically unveil Tremblay's double-dealing, thereby dismantling his credibility. With Tremblay's downfall, the conclave narrows its focus to Lawrence and Tedesco, each representing diverging paths for the Catholic Church.

Yet, as the fifth vote unfolds, tragedy strikes in the form of a suicide bombing in Rome, claiming 52 lives and damaging the sacred Sistine Chapel. In the ensuing chaos, Tedesco attributes blame to Islamists, advocating for an aggressive stance against Islam. This provocation inadvertently cues an enlightened retort from Benitez, condemning the conclave's fixation on politicking over authentic religious devotion. His earnest appeal strikes a chord among the cardinals, culminating in Benitez's unforeseen election as the new pope.

In the closing moments, Lawrence is privy to a shocking revelation: the former pope had orchestrated Benitez's visits to a gender reassignment clinic, a matter which could utterly compromise Benitez's position if publicized. Confronted, Benitez divulges that he is intersex, retaining both male and female reproductive organs. His forthright admission, "I am as God made me," resonates with Lawrence, who decides to protect Benitez's secret as a tribute to his allegiance with the late pope and his personal integrity. As the crowds rightfully acclaim the election of Pope Benitez, a beleaguered Lawrence gazes contemplatively from his window, embracing a newfound serenity amidst the turbulent conclave saga.