At the start of the 20th century, James Piper sets fire to his dead mother’s piano and heads out across Cape Breton Island to find a new place to live. Working as a piano tuner, he meets and eventually elopes with 13-year-old Materia Mahmoud, much to the anger of her wealthy, traditional Lebanese parents. James, madly obsessed with Materia, impregnates her, and then becomes increasingly frustrated and confused by her resulting strange behavior. Materia gives birth to their first daughter, Kathleen, and James subsequently becomes disgusted with his once intriguing wife, finally realizing that he actually married "a child". Materia regrets marrying James, and does not take to the child, as she believes her daughter's relationship with James to be revolting. James, however, is swollen with pride over his beautiful daughter, and spends his time ignoring and neglecting Materia while spoiling and smothering Kathleen. Through the eyes of James, his life is perfect, aside from his wife. According to the town folk, however, something appears to be seriously wrong with the Piper family. Materia is taken in by the kind neighbor Mrs. Luvovitz, who teaches her to sew and cook. Materia misses her old life and her family who have since disowned her. She grows to hate James and their daughter Kathleen.
Materia senses danger in James' obsession with their daughter and sees it as her duty to keep him distracted and occupied (especially in the bedroom), lest his affection for the young girl take an unnatural turn. Though his fixation on his eldest daughter is all encompassing, James eventually impregnates Materia three more times in quick succession. She gives birth to three girls, Mercedes, Frances and Lily, only to have newborn Lily die a crib death shortly after. She is from here on in the novel referred to as "Other Lily". The novel then explores the girls' relationship with their troubled father; their secretive, silent mother; and friendships that grow between them as they try to figure out their family's strange and mysterious history. As Kathleen grows older, she is perceived by her schoolmates as snobby, and they turn against her. Her father James is her only friend, and when he travels off to war, Kathleen is crushed. James, however, knows that he must leave Kathleen, as he has found himself increasingly attracted to her sexually. To him, enlisting is a way of beating "the devil."
Kathleen befriends her younger sisters, and James later returns as a shadow of his former self. Still, he feels an attraction to his eldest daughter, and he sends her to New York City to train with a highly regarded but challenging voice instructor and to fulfill her dream of becoming an opera singer at the Metropolitan Opera House. During her absence, James receives a letter from an "Anonymous Well-Wisher" suggesting that Kathleen may have gotten into trouble in New York. He immediately fetches her from New York, bringing her home where it becomes apparent that she is pregnant. Kathleen spends her pregnancy hidden in her family home, but eventually dies during childbirth, though her mother manages to save her twin children, a boy and a girl, by performing an emergency caesarian section. Influenced by her mother's increasing devotion to Catholicism, Kathleen's younger sister Frances believes the babies must be baptized, and so attempts to do so in the creek behind the house the night of their birth. James catches her, and believes she is trying to drown them. He drags her away and the male twin, named Ambrose by Frances, is accidentally left to drown in the creek. The female twin, Lily, contracts polio from the contaminated water in the creek, but survives the disease by what Mercedes attributes to a miracle. Mercedes, Frances and Lily are all raised to believe Materia is Lily's mother. When the accidental suicide of the grieving Materia shatters the world of the remaining Piper sisters, they come to depend on one another for survival. The development of the sisters — Kathleen, the promising diva; Mercedes, the caretaker; Frances, the mischievous one; and disabled Lily, the innocent one — forms the heart of the novel as they all bear the burden of their tragically flawed father.
At their mother's funeral, Frances is unable to stop herself from laughing at a private joke, and so covers her face with her hands. As a result, she is mistaken for sobbing and offered comfort, illustrating to the young girl how the truth of a situation can diverge from people's perception of it. After the baptism incident, Frances, beaten and all-but-disowned by her father, causes trouble in school, eventually getting herself expelled, despite Mercedes' best efforts to keep her in check. Frances finds solace in her dolls, matinee movies, her late mother's old hope chest, and her darling younger sister Lily. Frances eventually runs away in the middle of the night, ends up in a beaten down pub run by her Lebanese uncle, and becomes the pub's entertainment and pint-sized whore. She says she does it to save money for Lily, but Frances is unsure as to what exactly she is saving for. She discovers her long-lost grandfathers house, and then becomes obsessed with his African maid, Teresa. Frances, remembering fragments of what happened when her sister returned from the city, becomes convinced that Kathleen had taken a lover and become pregnant while away. She fixates on reenacting this aspect of her late sister's life. Eventually she stalks and seduces Teresa's brother, Leo, and becomes impregnated by him, after she has saved enough money for Lily and is ready to stop working. She dreams of becoming a mother to a black child, but her son, Aloysius, is pronounced dead at birth and she becomes depressed. After this trauma, Frances and her father slowly reconcile and she even becomes something akin to a confessor for him before he dies years later.
Lily is crippled, one of her legs being smaller than the other, and she wears a leather brace. She loves Frances the most of everyone, and was raised to believe Materia and James were her parents, although Frances liked to tell her otherwise. Lily believes everything Frances tells her, and so believes Ambrose is her guardian angel, and often wished for him to protect Frances after she left the house in the middle of the night. Lily said Ambrose lived in the creek, and he came to her in her dreams. Lily led Mercedes to the spot where Frances seduced Leo Taylor, and Mercedes believed that Lily was a saint.
Mercedes spends her time praying, taking care of the family and working hard at school. She flirts with the idea of a romance with the son of Mrs. Luvovitz, but drags her feet because his Jewish ancestry conflicts with her growing religious devotion and sense of propriety. Eventually he moves away, marries, and has children of his own, leaving her with nothing but repressed regret over both her snobbery and having never taken a chance on being happy. James, who has become a moonshiner as his primary income source, suffers a severe stroke and Mercedes is slowly consumed by her role as care-taker in the family; becoming severe and controlling as she gives up on any life for herself outside of this role. This culminates in her deception involving Frances' illegitimate mixed-race child: who was in fact given up for adoption by his disapproving aunt. As Frances and their father grow closer in his old age, Mercedes resents their bond, feeling left out and snubbed after all the sacrifices she has made for her family.
Kathleen's diary and old dress is eventually sent home by her caretaker in New York, and after Frances reads it, sends it with Lily to New York, to find Kathleen's lover. As Lily reads through the pages of the diary, we learn of Kathleen's vocal lessons, her instructor she calls the Kaiser, and her illicit love affair with the female black piano accompanist, Rose Lacroix. The romance is a whirlwind, as both women fall madly in love with one another, going to Jazz bars with Rose dressed as a man. Kathleen thrives, and basks in her complete happiness. The world is their oyster, until James barges into Kathleen's apartment one day to find her in bed with the black woman (whom he mistakes for a man). A furious attack on Rose leads to James' jealous rape of Kathleen, as his sexual desire for her finally overcomes him. This reveals Lily's true father, and James brings Kathleen home to Cape Breton, where she then dies in childbirth, her dreams shattered and her short and gloriously promising life cut terribly short. James eventually confesses everything to Frances, and soon after dies in his reading chair, peacefully. Frances finally reveals the family's darkest secrets to her sister Mercedes, who is firmly in denial. Frances dies as an elderly woman with the help of Mercedes, without ever knowing the actual fate of her child.
The novel ends in New York, as Lily makes her way across North America to Rose's apartment, where the ghostly return of her lover's doppelganger child pushes her over the edge. The two form a friendship and live together for many years, eventually to be visited by a young black man called Anthony, bearing a gift from Mercedes Piper. He delivers a drawing of a family tree, made by Mercedes, finally revealing all the incest, illegitimate children, crib deaths and affairs that make up the Piper family. Anthony is revealed to be Frances' long-lost son Aloysius, and Lily sits him down to tell him all about his mother.