At CERN, Father Silvano and Dr. Vittoria Vetra (Ayelet Zurer) created three canisters of antimatter. Silvano is murdered, and one of the canisters is stolen. The Catholic Church mourn the sudden death of Pope Pius XVI, and prepare for the papal conclave to elect his successor in Vatican City. Father Patrick McKenna (Ewan McGregor), the Camerlengo and a former helicopter pilot, takes control of the Vatican. Four of the "preferiti", the favoured candidates to be Pope, are kidnapped by a man claiming to represent the Illuminati. He sends the Vatican a warning, claiming he will murder each of the cardinals from 8 pm to midnight, when the stolen antimatter will explode and destroy the city, hidden somewhere within.
American symbologist Professor Robert Langdon (Tom Hanks) is brought to the Vatican to help. He deduces that the four cardinals will be murdered on the four altars of the "Path of Illumination", in locations relevant to the classical elements. McKenna gives Langdon access to the Vatican Secret Archives to research the altars, against the wishes of Commander Richter (Stellan Skarsgård), head of the Swiss Guard. He and Vittoria examine Galileo Galilei's banned book, following clues to the Chigi Chapel, accompanied by Ernesto Olivetti (Pierfrancesco Favino) and Claudio Vincenzi (David Pasquesi) of the Corps of Gendarmerie of Vatican City. They find Cardinal Ebner dead, having suffocated on a mouthful of dirt and branded with the ambigrammatic word "Earth".
The second, Cardinal Lamassé, is murdered in St. Peter's Square, his lungs punctured and branded with "Air". Vittoria comes to suspect the Pope was actually murdered via an overdose of tinzaparin and this is confirmed when McKenna secretly inspects the body in her presence. Langdon, Olivetti, and Vincenzi eventually identify the Santa Maria della Vittoria as the altar of fire, finding Cardinal Guidera burning to death, branded with “Fire”. The assassin appears, killing Olivetti and Vincenzi, before escaping to drown Cardinal Baggia (Marc Fiorini) in the Fontana dei Quattro Fiumi. Langdon intervenes and rescues Baggia with the help of bystanders. Baggia tells Langdon he was held with the preferiti in Castel Sant'Angelo.
Richter confiscates Dr. Silvano's journals, thus convincing Vittoria that he is a conspirator. Langdon, Vittoria, and the police storm Castel Sant'Angelo. Langdon and Vittoria find the assassin's lair, discovering five brands, the last meant for McKenna. The assassin (Nikolaj Lie Kaas) escapes, claiming his contractors are "men of God". Guided to a car by his unseen contractor, the assassin dies when the vehicle explodes upon ignition, as he has now become a loose end. Langdon and Vittoria find a secret passageway leading to the Vatican, warning the Swiss Guard of McKenna's fate. They find Richter hovering over a branded McKenna. He, and Archbishop Simeon, an alleged conspirator, are killed. Langdon retrieves a key from the dying Richter's hand.
The antimatter container is found in Saint Peter's tomb, due to detonate in five minutes, the cold temperature preventing its battery from being charged in time. McKenna seizes the canister, piloting a helicopter into the sky then parachuting out seconds before the antimatter detonates. McKenna is hailed as a hero, with calls for him to be elected Pope by acclamation.
Langdon and Vittoria retrieve Silvano's journals from Richter's office, finding he kept tabs on the Pope with hidden security cameras. Using the key Langdon retrieved from Richter, they find footage of Richter confronting McKenna, revealing that the Illuminati does not exist, and McKenna is the true mastermind behind the attacks. The Pope had invited Silvano to publicly present the antimatter as proof of a divine power, bridging the gap between religion and science. Considering such a claim blasphemy, McKenna orchestrated the Pope's death, and hired the assassin, plotting to have himself elected as Pope while making the Illuminati the scapegoat. The footage is shown to the papal conclave. McKenna, realizing he has been exposed, commits suicide via self-immolation, refusing to be taken alive.
The Vatican announces McKenna has died from injuries from his parachute landing, which leads to calls for Sainthood (since the people are not aware that he was the mastermind). Also announced is that Baggia is elected as Pope Luke I. Cardinal Strauss, the Pope's new Camerlengo, gives Langdon the "Diagramma Veritatis" as thanks for his help, and allows him to complete his scholarly work on Galileo and the history of the Illuminati. The new Pope gives Langdon and Vittoria a thankful nod, before stepping out on the balcony to greet the crowd below and give the traditional first blessing as Pope.
Tom Hanks as Robert Langdon
Ewan McGregor as Father Patrick McKenna
Ayelet Zurer as Dr. Vittoria Vetra
Stellan Skarsgård as Commander Maximilian Richter
Pierfrancesco Favino as Inspector General Ernesto Olivetti
Nikolaj Lie Kaas as The Assassin
Armin Mueller-Stahl as Cardinal Strauss
Thure Lindhardt as Lieutenant Chartrand
David Pasquesi as Claudio Vincenzi
Cosimo Fusco as Archbishop Simeon
Victor Alfieri as Lieutenant Valenti
Carmen Argenziano as Father Silvano Bentivoglio
Marc Fiorini as Cardinal Baggia/Pope Luke I
Bob Yerkes as Cardinal Guidera
Franklin Amobi as Cardinal Lamassé
Curt Lowens as Cardinal Ebner
Todd Schneider as a Carabiniere
Anna Katarina as Docent
Howard Mungo as Cardinal Yoruba
Rance Howard as Cardinal Beck
Steve Franken as Cardinal Colbert
Gino Conforti as Cardinal Pugini
Elya Baskin as Cardinal Petrov
August Wittgenstein as a Swiss Guard
based on Dan Brown's 2000 novel of the same title
the sequel to the 2006 film The Da Vinci Code