The action begins in Boeotia, at the Temple of Juno where the marriage of Semele, daughter of Cadmus, king of Thebes, and Athamas, a prince of Boeotia, is about to be solemnized.
Semele seems reluctant: she does not want to forgo her present liaison with Jupiter. Suddenly thunder is heard (a sign of Jupiter's activity), and the fire on the altar is extinguished: eventually the altar sinks from sight, and the wedding is abandoned in face of these omens. Ino, Semele's sister, reveals her love for Athamas, and Cadmus reports that, as his party was leaving Juno's temple, an eagle swooped down and carried Semele away; Jupiter now enjoys Semele's favours 'above' (--> Endless pleasure, endless Love).
Juno is incensed by Jupiter's affair with Semele, and she determines to destroy the woman who has displaced her. She decides that she will need help from Somnus, the god of sleep.
In her palace, Semele awakes (--> O Sleep, why dost thon leave me?).
Jupiter enters and the two renew their affection. But Semele is not entirely happy: she is only a mortal, and feels frightened when Jupiter leaves her. In order to distract Semele from wishing for immortality, Jupiter brings Ino to Semele for company: he transforms the scene to Arcadia (--> Where'er you walk) and leaves the sisters together to enjoy the harmony of the spheres.
Juno and her attendant messenger Iris visit Somnus' cave and (with some difficulty) awaken him. Among Juno's requests to Somnus is one that Ino should be immobilized by sleep so that Juno can impersonate her when she visits Semele: in return Juno guarantees to Somnus the lady that he desires, Pasithea.
Juno, disguised as Ino, goes to Semele; she asks whether Jupiter has consented to Semele's request to join the immortals. Semele replies that she is still mortal, and Juno gives her a mirror in order to admire her own features.
Semele gains confidence from what she sees in the mirror and Juno suggests that Semele should use her attractions to make Jupiter approach her bed "Not ... In Likeness of a Mortal, but like himself, the mighty Thunderer": by that means, Juno says, Semele will "partake of immortality" and be called from the mortal state.
Juno leaves as she hears Jupiter approach. Jupiter allows himself to be lured into promising to grant whatever Semele requests. When Semele asks him to appear "like Jove", Jupiter tries to dissuade her, but to no avail. Jupiter knows that if he appears as he really is, Semele will be consumed by his fire. And thus it turns out: Semele sees Jupiter afar in his true form, and dies. The chorus reflects on ambition that overreaches itself.
Ino, returned to the world of mortals, relates that in a dream Hermes told Ino that it was Jove's wish that she should now marry Athamas. Athamas enters willingly into the union.
A cloud descends on Mount Citheron, in which Apollo is discovered. He predicts that better times lie ahead, and specifically refers to the creation of Bacchus: "From Semele's ashes a Phoenix shall rise".