The first installment of the House of Teeth duology is set on Drepane, a fictional island governed by the Septinsular Covenant, a treaty imposed roughly a century earlier by Berengar, a knight from the mainland republic of Seraph. When a devastating plague struck Drepane, the island's seven noble houses discovered a ritual to raise the dead, but the resulting revenants terrorized both Drepane and Seraph. Berengar conquered the island, killed the doctors, priests, and prophets who knew the resurrection secret, burned their texts, and divided the body parts of every corpse among the seven houses to prevent reassembly. A caste of lay monks called leeches now oversees these desecrations.
The novel opens as the body of Adele-Blanche, the recently deceased Mistress of Teeth and ruling head of the noble House of Teeth, undergoes the mandatory desecration. Her granddaughter Agnes watches alongside her cousin Marozia, who has inherited the title. Agnes does not speak, a condition that puzzles everyone she meets. Prince Liuprand, eldest son of King Nicephorus the Sluggard, attends the ceremony. He addresses Agnes directly and seems puzzled when she does not respond, and before departing, his gaze lingers on her rather than on Marozia.
Agnes has been secretly trained by Adele-Blanche to perform the lost resurrection ritual. Her grandmother carved ascetic commandments into Agnes's skin and forced her to consume the flesh of her own half-brother, an infant born of her mother Celeste's forbidden affair. Celeste killed herself afterward. Agnes chose silence in the wake of these tortures, wielding muteness as defiance rather than enduring it as submission. Her mission is to accompany Marozia to Castle Crudele, the royal seat, arrange Marozia's marriage to Liuprand, and search the castle for the spell-words Berengar stole, so that Adele-Blanche can be resurrected.
At Castle Crudele, the cousins meet King Nicephorus, who is grotesquely obese, crude, and hostile. Waltrude, an elderly wet nurse who has served the royal family for decades, is assigned to attend them. Liuprand confronts Agnes in a corridor, demanding she speak and examining her mouth to confirm she has not been physically maimed. She remains silent, but his warmth unsettles her. When Agnes visits the castle library, Liuprand arrives, sits beside her, and recognizes her handwriting from the letter she composed on Marozia's behalf. He confirms the betrothal will proceed.
After the wedding, Marozia returns to Agnes in tears: Liuprand refused to touch her on their wedding night. Meanwhile, Agnes and Liuprand's bond deepens. He takes her to a hidden garden and teaches her a coded language Berengar devised using moths, in which each moth's color and pattern conveys a meaning: gray for grief, iridescence for love. Agnes is so charmed she forgets to plant her grandmother's henbane and mandrake seeds, herbs essential to the resurrection plot.
The king's cruelty escalates. When the House of Blood again fails to send representatives to a desecration, Nicephorus demands everyone in the hall declare him a true king. Agnes cannot speak to comply, and Nicephorus drives a knife through her hand repeatedly, destroying it so thoroughly she may never hold a quill again. Liuprand breaks free of the guards restraining him and stops the attack.
Nicephorus then decrees that Agnes will marry Lord Fredegar, the elderly Master of Blood, to mend the rift with that house. To make her a worthy bride, the king transfers the title Mistress of Teeth from Marozia to Agnes. Marozia is devastated.
At the House of Blood, Fredegar proves gentle and noble, assuring Agnes that her silence will never trouble him. Freed from Marozia's shadow and Adele-Blanche's ghost, Agnes sees her own beauty for the first time and breaks every ascetic rule carved into her skin. On their wedding night, however, Fredegar's son Unruoching ambushes them and stabs his father to death, then turns his blade on Agnes. She screams, breaking years of silence, and calls Liuprand's name. The Dolorous Guard, the Crown's armed royal guard, arrests Unruoching, and Liuprand sentences him to be walled up alive.
That night, Agnes speaks to Liuprand for the first time. They confess their love and make love. Agnes shows him the scars covering her body, and he calls her beautiful.
Back at Castle Crudele, Nicephorus reveals that both the House of Blood and the House of Eyes have withdrawn their loyalty, since Unruoching's wife Ygraine is the daughter of Lord Thrasamund, the Master of Eyes. The king decrees that Liuprand must consummate his marriage with Marozia at once: She must produce a daughter to be betrothed to Gamelyn, Unruoching's young son and new Master of Blood.
Nine months later, Marozia delivers twins: a girl, Meriope, and a boy, Tisander. Nicephorus decrees that Tisander is heir to the throne and Meriope will be wed to Gamelyn as planned. Marozia rejects the boy, and Agnes takes the infant, falling instantly in love. The leech Pliny, who long served Lord Fredegar, discovers Agnes and Liuprand's ongoing affair but does not condemn them. Instead, he performs a secret wedding ceremony in the dead language of Seraph, with Waltrude as witness.
Seven years pass. Agnes raises Tisander while Marozia remains isolated in her tower with her handmaiden Ninian, who is deeply in love with her mistress. For the celebration of Meriope's wedding to Gamelyn, Agnes writes and produces an elaborate masque that proves a triumph. During the feast, however, Childeric, son of Lord Thrasamund, proposes marriage to Agnes and grabs her wrist when she refuses. Liuprand, drunk on wine, beats Childeric so savagely that Childeric is left permanently disabled. Thrasamund renounces his loyalty to the Crown, and Meriope is seized from Marozia's arms. Marozia chases Agnes onto a crumbling parapet and strangles her, accusing Agnes of stealing everything: title, beauty, children, and husband. Liuprand pulls Agnes to safety as the stone collapses beneath them.
Agnes secretly sends a letter to Thrasamund, signed with Liuprand's name, and offers to marry Childeric herself, providing the House of Eyes with a bride of the highest pedigree. Liuprand is anguished but cannot dissuade her.
The betrayal unfolds swiftly. Ninian, acting on Marozia's orders, coordinates with Thrasamund and opens Castle Crudele's gates to his armed forces. Agnes waits alone in the chapel where she and Liuprand meet in secret. Thrasamund's men burst in, force her to her knees, and Thrasamund slits her throat. Liuprand arrives too late. Stabbed in the thighs, he crawls to Agnes's body. In an act of calculated degradation, Thrasamund's men force the grief-maddened prince into coupling with Agnes's corpse to prove his desire was base rather than noble. Thrasamund declares the overthrow of Castle Crudele.
Agnes's body is sealed in a stone vault deep beneath the castle, the first corpse on Drepane in a century to be preserved rather than desecrated. In the final lines, something stirs in her womb, the womb Adele-Blanche's rituals had rendered permanently barren. Whether this is the latent effect of her grandmother's sorcery, the castle's buried magic, or the transcendent power of Seraphine love, the novel does not say. The story continues in the duology's second book.