The novel opens with Clara as a young girl, writing in her first journal about the arrival of a new pet, an enormous dog that she names Barrabás. Clara continues to write in journals the rest of her life, and it's thanks to her and these journals that the narrator can piece together the family history fifty years later.
The story officially opens on Holy Thursday during the time of Lent in the Chilean countryside. A ten-year-old girl named Clara del Valle sits in church with her family while the priest, the bombastic Father Restrepo, leads services. Clara's parents are not avid churchgoers; Severo del Valle is an atheist and Nívea del Valle prefers personal communion with God, yet they must attend church to keep up appearances. Nívea and Severo have eleven living children. Their eldest daughter, Rosa, attracts attention wherever she goes, church being no exception. She was born with a strange and mermaid-like beauty, having green hair, yellow eyes, and almost translucent skin. She is engaged to a young miner named Esteban Trueba, who is trying to make his fortune in a faraway mine. Suddenly Clara breaks the silence in the church by saying: "Psst! Father Restrepo! If that story about hell is a lie, we're all fucked, aren't we..." to which Father Restrepo replies by pronouncing Clara to be possessed by the devil. While severe, Father Restrepo's pronouncement about Clara is not entirely off-base because Clara is clairvoyant and can move objects with her mind.
After church, the body of the eccentric Uncle Marcos is dropped off at the del Valle household. Uncle Marcos was an eccentric traveler who resembled a pirate. His most famous expedition was into the mountains on an airplane he made himself. After he disappeared for much longer than expected, he was presumed dead and a funeral was held, but then he made a grand return, after which he became a mentor for Clara. She was enthralled by his stories and his collection of books and magical objects. When Uncle Marcos's corpse is delivered to the del Valle household, Clara insists on keeping a decrepit puppy that is among his belongings. She names him Barrabas and he grows into a gargantuan dog that eats or knocks over everything in sight.
Esteban Trueba is a young, ambitious entrepreneur who is engaged to the eldest del Valle daughter, Rosa the beautiful. He slaves away in a mine in the North, hoping to make his fortune so he can return to the capital to marry Rosa. Unfortunately, Rosa dies before he can strike it rich, poisoned by a swig of brandy that was intended to kill her father, a liberal politician. Everyone is devastated by her death, especially Esteban. Clara stops speaking for the next nine years because she worries that, by predicting Rosa's death, she is the one who caused it.
The story shifts to Esteban's family life. His sister, Férula, is sacrificing her youth to care for their ailing mother, Doña Ester. After spending many months mining, Esteban decides to make a living by restoring their ruined family estate, Tres Marías. When Esteban arrives, he finds that the master house is just as it was when he was a child, but is now weathered and filthy. Generations of servants live on the property in squalor. Pedro Segundo García, a man about the same age as Esteban, has been acting as their leader in the absence of a patron. The servants immediately accept Esteban as their new patron and he begins a "new life that, in time, would make him forget Rosa." As an old man, Esteban is adamant that he was a good patron because he improved the standard of life at Tres Marías, even though he treated the servants badly in many ways.
Esteban soon feels at home at Tres Marías, but he is "slowly becoming a barbarian," overcome by his sexual urges. One day, he rapes Pedro Segundo Garcia’s sister, Pancha García. Afterwards, he allows her to work in the house as his mistress instead of in the fields. At the same time, he begins to work more...