A noble young Roman maiden named Cecilia, a Christian from birth, is engaged to be married to a man named Valerian. Cecilia, however, hopes to remain a virgin all her life, and prays to God to make it so. On her wedding night, she offers to tell her new husband a secret if he promises not to betray her. When he agrees, she tells him that she has an angel protecting her chastity. If her new husband attempts to take her virginity, this angel will smite him dead. If, however, he loves Cecilia chastely, the angel will love him as he loves her. Valerian asks to see the angel as a token that he should trust her, but Cecilia tells him he can only see it if he becomes a Christian. She sends Valerian to be baptized at the hands of Pope Urban, who rejoices at the holy work Cecilia has done. A spirit appears holding a book with gold letters. After reading the words of gold that proclaim God and Christianity, Valerian assents to them as true and receives baptism.
Upon his return to his bedchamber, Valerian is able to see Cecilia's angel. The angel crowns both of them with sweet-smelling rose and lily crowns, and then offers to grant one request of Valerian's. Valerian asks that his brother Tiburtius be brought to the true faith, and the angel assents. Immediately, Tiburtius walks into the room and wonders at the sweet smell within it, which pierces him to the core. Valerian explains that the smell emanates from invisible crowns of roses and lilies, which Tiburtius will be able to see if he embraces the truth. Then Cecilia shows her brother-in-law the truth of Christianity, and Tiburtius expresses a desire to be baptized. Rejoicing, Cecilia and Valerian tell him he must go to Pope Urban. When Tiburtius expresses fear that anyone who associates with Urban, who is a wanted man, will be burned, Cecilia comforts him with Christ's promise of another life after this earthly one. Finally, Tiburtius meets Pope Urban and is baptized.
After a time, the Roman prefect Almachius declares that all those who refuse to worship at the shrine of Jupiter will be killed. Valerian and Tiburtius, taken to the shrine, refuse to sacrifice to Jupiter and are thus sentenced to be executed. The executioner Maximus, however, upon hearing their Christian teachings, takes them back to his home to hear more. After a night of preaching, Cecilia arrives with priests, and Maximus and all his household receive baptism. The brothers Valerian and Tiburtius return to the shrine of Jupiter, where they refuse to worship and are executed. Testifying that he saw the brothers' souls glide to heaven, Maximus arouses Almachius's anger and also gets beheaded. Cecilia buries him next to her brothers.
Almachius orders Cecilia brought before him. They engage in a lengthy conversation in which Almachius expresses outrage at Cecilia's refusal to worship his gods or cower before his power. Cecilia's response is that she and everyone know the true faith and that Almachius is foolish. She asserts that Almachius's gods are made of stone, and that God, not Almachius, has power over people's lives. Furious, Almachius sentences Cecilia to death by boiling.
Almachius's henchmen take Cecilia back to her house where they light a fire under a pot of boiling water with Cecilia in it. Despite the great heat, Cecilia does not even feel uncomfortable, and survives for a day and night in the hot cauldron. Almachius sends his executioner to kill Cecilia with a sword. Despite taking three strokes, however, the man is unable to kill her, and is prevented by law from taking a fourth stroke. Thus Cecilia continues to live, spurting blood and with her head partially severed from her body, for three days.
During this time, Celia continually preaches to and teaches the people. She gives them her possessions and recommends their souls to Pope Urban. She also asks Pope Urban to make her home into a church. Then she dies. Pope Urban fetches her body by night and buries it next to those of his other saints. He sanctifies Cecilia's home as the Church of Saint Cecilia.