The story starts with the del Valle family, focusing upon the youngest and the oldest daughters of the family, Clara and Rosa. The youngest daughter, Clara del Valle, has paranormal powers and keeps a detailed diary of her life. Using her powers, Clara predicts that an accidental death will occur in the family. Shortly after this, Clara's sister, Rosa the Beautiful, is killed by poison intended for her father who is running for the Senate. Clara is shocked into muteness after witnessing the autopsy performed on her sister's body. Rosa's fiancé, a poor miner named Esteban Trueba, is devastated and attempts to mend his broken heart by devoting his life to restoring his family hacienda, Las Tres Marías, which has fallen into poverty and disrepair. He sends money to his spinster sister who takes care of their arthritic mother in town. Through a combination of intimidation and reward, he enforces respect and labor from the fearful peasants and turns Tres Marías into a "model hacienda". He turns the first peasant who spoke to him upon arrival, Pedro Segundo, into his foreman, who quickly becomes the closest thing that Trueba ever has to an actual friend during his life. He rapes many of the peasant women and children, and his first victim, then 15 year old Pancha García, becomes the mother of his bastard son, Esteban García. Throughout the novel, he visits Transito Soto, a prostitute. With Esteban's help, she becomes a wildly successful brothel madam in the city and always is willing to repay the favor to him.
Esteban returns to the city to see his dying mother. After her death, Esteban decides to fulfill her dying wish for him to marry and have legitimate children. He goes to the Del Valle family to ask for Clara's hand in marriage. Clara accepts Esteban's proposal; she herself has predicted her engagement two months prior, speaking for the first time in nine years. During the period of their engagement, Esteban builds what everyone calls "the big house on the corner," a large mansion in the city where the Trueba family will live for generations. After their wedding, Esteban's sister Férula comes to live with the newlyweds in the big house on the corner. Férula develops a strong dedication to Clara, which fulfills her need to serve others. However, Esteban's wild desire to possess Clara and to monopolize her love causes him to throw Férula out of the house. She curses him, telling him that he will shrink in body and soul, and die like a dog. Although she misses her sister-in-law, Clara is unable to find her by any means - the gap between her and her husband widens as she devotes more time to her daughter and the mystic arts.
Clara gives birth to a daughter named Blanca and later, to twin boys Jaime and Nicolás. The family, which resides in the capital, stays at the hacienda during the summertime. Upon arriving at Tres Marías for the first time, Blanca immediately befriends a young boy named Pedro Tercero, who is the son of her father's foreman. Blanca and Pedro grow up together as best friends despite them being of two different social and economic classes. During their teenage years, Blanca and Pedro Tercero eventually become lovers. After an earthquake that destroys part of the hacienda and leaves Esteban injured, the Truebas move permanently to Las Tres Marías. Clara spends her time teaching, caring for her husband's battered body, and writing in her journals while Blanca is sent to a convent school and the twin boys back to an English boarding school, both of which are located in the city. Blanca fakes an illness so as to be sent back to Las Tres Marías, where she can be with Pedro Tercero, but when she arrives home she finds that Pedro Tercero has been banished from the hacienda by Esteban on account of his revolutionary socialist ideas. Pedro Tercero meets with Blanca in secret adopting disguises while also spreading his ideas in the form of song to neighboring haciendas.
A visiting French count to the hacienda, Jean de Satigny, reveals Blanca's nightly romps with Pedro Tercero to her father. Esteban furiously goes after his daughter and brutally whips her. When Clara expresses horror at his actions, Esteban slaps her, knocking out her front teeth. Clara decides to never speak to him again, reclaims her maiden name and moves out of Tres Marías and back to the city, taking Blanca with her. Esteban, furious and lonely, blames Pedro Tercero for the whole matter; putting a price on the boy's head with the corrupt local police. At this point, Pedro Segundo deserts Esteban, telling him he does not want to be around when Trueba inevitably catches his son. Enraged by Pedro Segundo's departure, Trueba begins hunting for Pedro Tercero himself, eventually tracking him down to a small shack near his hacienda. He only succeeds in cutting off three of Pedro's fingers, and is filled with regret for his uncontrollable furies.
Blanca finds out she is pregnant with Pedro Tercero's child. Esteban, desperate to save the family honor, gets Blanca to marry the French count by telling her that he has killed Pedro Tercero. At first, Blanca gets along with her new husband, but she leaves him when she discovers his participation in sexual fantasies with the servants. Blanca quietly returns to the Trueba household and gives birth to her daughter, Alba. Meanwhile, Jaime and Nicholas both fall in love with a young drug addict named Amanda; Amanda initially loves Nicholas and becomes pregnant with his child. Jaime has to perform an abortion, ruining his relationship with Nicholas. Amanda and her little brother Miguel stay for a short time at the Trueba house; Miguel is able to witness Alba's birth, his future lover.
Esteban Trueba eventually moves to the Trueba house in the capital as well, although he continues to spend periods of time in Tres Marías. He becomes isolated from every member of his family except for little Alba, whom he is very fond of. Esteban runs as a senator for the Conservative Party but is nervous about whether or not he will win. Clara speaks to him, through signs, informing him that "those who have always won will win again" – this becomes his motto. Clara then begins to speak to Esteban through signs, although she keeps her promise and never actually speaks to him again. A few years later, Clara dies peacefully and Esteban is overwhelmed with grief.
Alba is a solitary child who enjoys playing make-believe in the basement of the house and painting the walls of her room. Blanca has become very poor since leaving Jean de Satigny's house, getting a small income out of selling pottery and giving pottery classes to mentally ill children, and is once again dating Pedro Tercero, now a revolutionary singer/songwriter. Alba and Pedro are fond of each other, but do not know they are father and daughter, although Pedro suspects this. Alba is also fond of her uncles. Nicolás is eventually kicked out by his father, supposedly moving to North America.
When she is older, Alba attends a local college where she meets Miguel, now a grown man, and becomes his lover. Miguel is a revolutionary, and out of love for him, Alba involves herself in student protests against the conservative government. After the victory of the People's Party (a socialist movement), Alba celebrates with Miguel.
Fearing a Communist dictatorship, Esteban Trueba and his fellow politicians plan a military coup of the socialist government. However, when the military coup is set into action, the military men relish their power and grow out of control. Esteban's son Jaime is killed by power-driven soldiers along with other supporters of the government. After the coup, people are regularly kidnapped and tortured. Esteban helps Blanca and Pedro Tercero flee to Canada, where the couple finally find their happiness.
The military regime attempts to eliminate all traces of opposition and eventually comes for Alba. She is made the prisoner of Colonel Esteban García, the son of Esteban Trueba's and Pancha Garcia's illegitimate son, and hence the grandson of Esteban Trueba. During an earlier visit to the Trueba house, García had molested Alba as a child. In pure hatred of her privileged life and eventual inheritance, García tortures Alba repeatedly, looking for information on Miguel. He rapes her, thus completing the cycle that Esteban Trueba put into motion when he raped Pancha García. When Alba loses her will to live, she is visited by Clara's spirit who tells her not to wish for death, since it can easily come, but to wish to live. She becomes to write down her family's story in her mind.
García, fearful of his growing attachment to Alba, discards her. Esteban Trueba manages to free Alba with the help of Miguel and Tránsito Soto, his old friend and the brothel madam. After helping Alba write their memoir, Esteban Trueba dies in the arms of Alba, accompanied by Clara's spirit; he is smiling, having avoided Férula's prophecy that he will die like a dog. Alba is pregnant, though whether the child is Miguel's or the product of her rape is unknown. Alba embraces this ambiguity, however, loving her unborn child as above all, it is her own. Alba resolves that she will not seek vengeance on those who have injured her, choosing to believe in the hope that one day the human cycle of hate and revenge will be broken. Alba is revealed to be the narrator of the novel, which she writes while she waits for Miguel and for the birth of her child.
