The young Roman patrician Marcus Vinicius falls in love with Lygia, a barbarian hostage being raised in the house of the retired general Aulus Plautius. Vinicius' courtier uncle Petronius uses his influence with the Emperor Nero to have Lygia placed in Vinicius' custody. But first, Nero forces her to appear at a feast on the Palatine Hill. Secretly a Christian after having been converted by Plautius' wife Pomponia Graecina, Lygia is appalled by the degenerate Roman court. She is rescued by her fellow Christians while being escorted to Vinicius' house the following day, and disappears.
Petronius takes pity on the desolate Vinicius, and hires the cunning Greek philosopher Chilo Chilonis to help him find Lygia.[10] Chilo soon establishes that Lygia was Christian, and goes undercover in the Christian community in Rome to find her. When he tells Vinicius that the entire Christian community is going to meet at night outside the city to hear the apostle Peter, Vinicius insists on attending the meeting himself in hope of seeing Lygia there. At the meeting, a disguised Vinicius is strangely touched by Peter's words, but forgets everything when he sees Lygia. He traces Lygia to her hiding place in Transtiber Rome, but is stopped and severely wounded by her barbarian bodyguard Ursus when he goes in to kidnap her.
Instead of killing Vinicius, Lygia and her Christian friends take him in and nurse him back to health.[11] At this point Lygia falls in love with him, and confides in the Apostle Paul. He tells her that she cannot marry a non-Christian, so she leaves Vinicius' bedside and disappears a second time.
After returning to health, Vinicius is a changed man. He starts treating his slaves with more kindness, and rejects the advances of the depraved empress Poppaea Sabina. When Chilo brings him information of Lygia's new hiding place and advises him to surround the house with soldiers, Vinicius has him whipped. Chilo swears revenge while Vinicius goes to Lygia's hiding place alone. After promising Lygia's guardians, the apostles Peter and Paul, to convert, he is engaged to Lygia with their blessing.
The emperor Nero and his court, including Vinicius, go to Antium for recreation. Nero is composing a poem about the burning of Troy, and expresses regret at never having seen a real city burning. Later, the courtiers are shocked when news comes that Rome is aflame. Vinicius rides back to Rome to save Lygia, and Peter baptizes him on the spot after he rescues him and Lygia from the flames.
When Nero returns to Rome and sings his poem about Troy in public, the masses accuse him of igniting the fire. Nero's advisors decide they need a scapegoat. The Prefect of the Praetorian Guard, Tigellinus, suggests the Christians. It is revealed that the idea has been given to him by Chilo, still desperate for revenge on Vinicius after his whipping. Vinicius' uncle Petronius protests, but the empress Poppaea—still nursing a grudge against Vinicus for spurning her advances—overrules him.
Chilo divulges the Christians's hiding place to the authorities, and many of the Christians are arrested, including Lygia. Nero has planned a series of games in the arena, at which the Christians will be butchered in "revenge" for the fire. But even the Roman mob is shocked by the cruelty of the exhibitions: in the penultimate show, Christians are set alight on crosses to illuminate a luxurious feast open to the Roman public. Chilo is so appalled by the scene that he repents and publicly accuses Nero of igniting the fire. As the court scatters, Paul emerges from the shadows and promises Chilo salvation if he truly repents. This gives Chilo the courage to die bravely in the arena the following day, after refusing to retract his accusation.
Meanwhile Lygia and her bodyguard Ursus have been kept for the final show, in which they are exposed to an aurochs in the arena,[12] but when Ursus manages to break the animal's neck, the crowd is impressed and forces Nero to spare the two. She is then married to Vinicius, and the two move away to the latter's mansion in Sicily where they live openly as Christians.
The rest of the novel relates the historical events of Peter's martyrdom ("Quo vadis, Domine?"), Petronius' suicide in the aftermath of the Pisonian conspiracy, and concludes with an account of Nero's ultimate death based on Suetonius.
