In the Chatham Islands, of the coast of New Zealand, Adam Ewing writes in his journal about meeting a strange doctor named Henry Goose. The two become friends. While on the island, Adam learns about the history of the Moriori people, who existed peacefully on the island until the Maori came and attacked them, killing many Moriori and enslaving those who remained. One day, Adam witnesses some villagers whipping a tied-up Moriori man. As Adam leaves aboard the Prophetess, he finds a Moriori stowaway in his cabin. The stowaway is Autua—the Moriori man whose whipping Adam witnessed. After some hesitation, Adam agrees to help Autua, and he convinces the captain of the ship to take Autua to Hawaii. While aboard the ship, Adam begins to suffer from severe headaches. Dr. Henry Goose diagnoses him with a brain parasite and offers a cure, but Adam’s condition only worsens.
Many years later, in a remote part of Belgium near Bruges, the young composer Robert Frobisher writes letters to Rufus Sixsmith. Robert’s father recently disinherited him, and so, in order to win back his father’s respect, Robert decides to become the assistant of Vyvyan Ayrs, a famous British composer who is blind and hasn’t composed any new work in several years. While living with Ayrs, Robert discovers and reads the first part of Adam Ewing’s journal. Though Ayrs and Robert don’t get along at first, Robert ultimately helps Ayrs create some unusual late-career works.
Later, in California in the 1970s, Rufus Sixsmith, an engineer at a nuclear plant located on Swannekke Island, still holds on to Robert’s letters. Rufus he warns gossip-column journalist Luisa Rey that Seaboard Power (the company behind the nuclear plant) is trying to cover up the risk of a deadly accident at the plant. Soon after, Robert ends up dead. Though authorities rule his death a suicide, Luisa believes it’s murder and investigates the story. In the process, she draws the attention of Seaboard Power, and the company hires an assassin to ram Luisa’s car off a bridge, seemingly killing her.
As it turns out, Luisa’s whole story is a manuscript that comes across the desk of Timothy Cavendish, the sixty-something owner of a vanity publishing company in London. None of Timothy’s books sells well until the day when one of his authors, Dermot Hoggins, throws a famous literary critic off a roof, killing him. This act turns Dermot into a famous murderer, and sales of his memoir, Knuckle Sandwich, go through the roof, making Timothy a lot of money. But when Dermot’s brothers come to try to extort more money from Timothy, Timothy asks his brother Denholme Cavendish for help. Denholme tricks Timothy into committing himself to a nursing home called Aurora House, located outside London. Soon after he realizes he’s trapped in Aurora House, Timothy has a stroke.
The events of Timothy Cavendish’s life so far make up the first half of a film that exists in a futuristic version of Korea, where a “fabricant” (synthetically created human clone) named Sonmi~451 awaits execution by the “corpocratic” (hyper-capitalist) government. An interviewer known only as the Archivist asks Sonmi questions about her past. Sonmi tells the Archivist that she used to know practically nothing about the world around her and worked at a restaurant chain called Papa Song’s—until a fellow fabricant named Yoona~939 helped Sonmi learn to read and “ascend” to a higher state of intelligence. After Yoona dies during a botched escape attempt, Sonmi becomes a research subject at a university and continues to read and learn more about the world.
Many years after her death, Sonmi survives as a goddess to the Valleysmen people of a remote Pacific Island; the Valleysmen survived a nuclear apocalypse and now live hunter-gatherer lives without advanced technology. But when Valleysman Zachry has a crisis of faith when he meets Meronym, a woman from the technologically advanced Prescient people. Meronym stays with the Valleysmen to observe them. She has an egglike object called an “orison” that contains a recording of Sonmi’s interview with the Archivist. Zachry’s Pa died at the hands of a rival tribe called the Kona, and just before Meronym leaves the Valleysmen, the Kona attack again, capturing Zachry. Although Meronym initially intends to observe the Valleysmen without interfering in their lives, she breaks her promise to save Zachry. Together, the two of them venture across the island to meet up with one of Meronym’s Prescient allies. Zachry tells this story to future generations of Valleysmen, and many of them wonder how much of his story is true. One of Zachry’s descendants watches the orison that contains the rest of Sonmi’s interview.
At the university, Sonmi gets involved with an anti-government rebel group called the Union. While working with the Union, Sonmi learns that fabricants like her don’t get to retire after their 12 years of service but in fact get butchered and turned into food. She writes a manifesto against the government called Declarations, but shortly after completing it, government agents swoop in to capture her. As she awaits execution, Sonmi wonders whether the Union was a true resistance group or whether it was all part of a government conspiracy to turn people against fabricants. For her last request, Sonmi asks to see the end of Timothy Cavendish’s movie.
After slowly recovering from his stroke, Timothy decides he must escape Aurora House. He develops a scheme with fellow nursing home residents Ernie Blacksmith and Veronica Costello, and together they steal a car and escape. Timothy manages to return to his old life in publishing, where the first thing he does is request the end of the manuscript for Half-Lives: The First Luisa Rey Mystery.
As it turns out, Luisa Rey manages to survive when her car crashes into the water, but she loses the documents that prove Seaboard Power’s dangerous negligence. She continues pursuing the story, even as agents from Seaboard continue to threaten her life. Ultimately, she gets a tip from Megan (Rufus Sixsmith’s niece) about how to find a backup copy of her uncle’s documents. The story goes to print, finally exposing Seaboard’s corruption. Afterward, Megan sends Luisa the remaining letters from Robert that belonged to Rufus.
In Belgium, Robert continues working with Ayrs, but he becomes even more interested in his own work, the Cloud Atlas Sextet. When Ayrs attempts to plagiarize Robert’s work and pass it off as his own, the two “divorce,” and Robert leaves. After completing the Cloud Atlas Sextet, Robert mails a final letter to Rufus where he announces that he’s about to kill himself. Robert includes the rest of The Pacific Journal of Adam Ewing in his letter to Rufus.
The narrative returns to Adam Ewing as he sails on the Prophetess toward Hawaii. His condition hasn’t improved, and Dr. Henry Goose’s supposed “cure” doesn’t seem to be working. After overhearing a conversation between Henry and Autua, Adam realizes that Henry is trying to poison him to get his money. Adam tries to confront Henry, but he’s too weak and passes out. When Adam regains consciousness, he finds that Autua has saved him, and Henry is gone. Adam decides to devote the rest of his life to fighting against the predatory side of human nature. A later note from Adam’s son states that this is the part of the journal where Adam’s handwriting stops being intelligible.
