The book consists of six nested stories; each is read or observed by the protagonist of the next, progressing in time through the central sixth story. The first five stories are each interrupted at a pivotal moment. After the sixth story, the others are resolved in reverse chronological order.
The Pacific Journal of Adam Ewing (Part 1)
The first story begins in the Chatham Islands near New Zealand in the mid-nineteenth century, where Adam Ewing, a guileless American lawyer from San Francisco during the California Gold Rush, awaits repairs to his ship. He witnesses a Moriori slave being flogged by a Maori overseer. During the punishment, the victim, Autua, sees pity in Ewing's eyes and smiles. As the ship gets underway, Dr. Henry Goose, Ewing's only friend aboard the ship, examines Ewing’s chronic ailment. The doctor diagnoses Ewing with fatal parasite infection and recommends a course of treatment. Meanwhile, Autua has stowed away in Ewing's cabin. When Ewing discloses this to the Captain, Autua proves himself a first-class seaman, and the Captain puts Autua to work for his passage to Hawaii.
Letters from Zedelghem (Part 1)
The next story is set in Zedelghem, near Bruges, Belgium, in 1931. It is told in the form of letters from Robert Frobisher, a recently disowned and penniless young English musician, to his lover Rufus Sixsmith. Frobisher journeys to Zedelghem to become an amanuensis to the reclusive once-great composer Vyvyan Ayrs, who is dying of syphilis and nearly blind. Soon, Frobisher produces Der Todtenvogel ("The Death Bird") from a basic melody that Ayrs gives him. It is performed nightly in Kraków, and Ayrs is much praised. Frobisher takes pride in this and begins composing his own music again. Frobisher and Ayrs' wife Jocasta become lovers, but her daughter Eva remains suspicious of him. Frobisher sells rare books from Ayrs' collection to a fence, but is intrigued by reading the first half of The Pacific Journal of Adam Ewing, and asks Sixsmith if he can obtain the second half so Frobisher can learn how the story ends. Ayrs asks Frobisher to write a song inspired by a dream of a "nightmarish cafe", deep underground, wherein "the waitresses all had the same face" and ate soap.[1] As the summer comes to an end, Jocasta thanks Frobisher for "giving Vyvyan his music back", and Frobisher agrees to stay until the next summer.
Half-Lives: The First Luisa Rey Mystery (Part 1)
The third story is written in the style of a mystery/thriller novel, set in the fictional city of Buenas Yerbas, California, in 1975, with protagonist Luisa Rey, a young journalist. She meets the elderly Rufus Sixsmith in a stalled elevator, and she tells him about her late father, one of the few incorruptible policemen in the city, who became a famous war correspondent. Later, after Sixsmith tells Luisa his concern that the Seaboard HYDRA nuclear power plant is not safe, he is found dead of apparent suicide. Luisa believes the businessmen in charge of the plant are assassinating potential whistleblowers. From Sixsmith's hotel room, Luisa acquires some of Frobisher's letters. Another plant employee, Isaac Sachs, gives her a copy of Sixsmith's report. Before Luisa can report her findings on the nuclear power plant, a Seaboard-hired assassin who has been following her forces her car—along with Sixsmith's incriminating report—off a bridge.
The Ghastly Ordeal of Timothy Cavendish (Part 1)
The fourth story, comic in tone, is set in Britain in the early twenty-first century; Timothy Cavendish, a 65-year-old vanity press publisher, flees the brothers of his gangster client, whose book is experiencing high sales after the murder of a book critic. They threaten Cavendish with violence if their monetary demands are not met. Cavendish's wealthy brother, exasperated by Cavendish's frequent previous pleas for financial aid, books him into a menacing nursing home. Timothy signs custody papers, thinking that he is registering at a hotel where he can stay until his personal and financial problems can be solved. When he realizes he will be held there indefinitely, subject to the staff's complete control, he tries to flee but is stopped by a security guard and confined. He briefly mentions reading a manuscript titled Half-Lives: The First Luisa Rey Mystery, but is not initially impressed by the prospective author's manuscript and only comes to appreciate it later. He settles into his new surroundings while still trying to plot a way out. One day, he has a stroke, and the chapter ends.
An Orison of Sonmi-451 (Part 1)
The fifth story is set in Nea So Copros,[2] a dystopian state in twenty-second century Korea, derived from corporate culture. It is told in the form of an interview of Sonmi-451, after her arrest and trial, by an "archivist" who records Sonmi-451's story into an 'orison', a silver egg-shaped device for recording and holographic videoconferencing. Sonmi-451 is a fabricant waitress at a fast-food restaurant called Papa Song's. Clones grown in vats are revealed to be the predominant source of cheap labor. The "pureblood" (natural-born) society hinders the fabricants' consciousness by chemical manipulation using a food Sonmi refers to as "Soap". After twelve years as slaves, fabricants are promised retirement to a fabricant community in Honolulu. In her own narration, Sonmi encounters members of a university faculty and students, who take her from the restaurant for study and assist her to become self-aware, or "ascended". She describes watching The Ghastly Ordeal of Timothy Cavendish as a pre-Skirmishes film (wherein the "Skirmishes" are a major global disaster or war that destroyed most of the world except Nea So Copros). During the scene in which Cavendish suffers his stroke, a student interrupts to tell Sonmi and her rescuer Hae-Joo Im that Professor Mephi, Hae-Joo's professor, has been arrested, and that policy enforcers have orders to interrogate Hae-Joo and kill Sonmi on sight.
Sloosha's Crossin' an' Evrythin' After
The sixth story occupies the central position in the novel and is the only one not interrupted. On the Big Island of Hawaii after a great societal collapse, the Valley Folk are peaceful farmers who worship a goddess called Sonmi. Zachry Bailey is plagued by moral doubts stemming from blaming himself for his father's death and the kidnapping of his brother years prior. Big Island is occasionally visited and studied by a technologically sophisticated people known as the Prescients, one of whom, Meronym, visits Zachry’s village to his suspicion. When Meronym later requests a guide to the top of Mauna Kea volcano, Zachry reluctantly agrees, citing his debt to her for saving his sister Catkin from poisoning. They climb to the ruins of the Mauna Kea Observatories, where Meronym explains the orison Zachry found in her room and reveals Sonmi's history (as introduced in the prior chapter). Upon their return, they go with most of the Valley Folk to trade at Honokaa, but Zachry's people are attacked and imprisoned by the cannibalistic Kona tribe, who often raid the Valley Folk and are conquering the territory. Zachry and Meronym eventually escape, and she takes him to a safer island. The story ends with Zachry's child recalling that his father told many unbelievable tales, but that this one may be true because he has inherited Zachry's copy of Sonmi's orison.
An Orison of Sonmi-451 (Part 2)
Hae-Joo Im reveals that he and Mephi are members of an anti-government rebel movement called Union. Hae-Joo then guides Sonmi in disguise to a ship, where Sonmi witnesses retired fabricants butchered and recycled into Soap, the fabricant food source. Any leftover "reclaimed proteins" from the butchered fabricants are used to produce food that purebloods unknowingly consume at fast-food type restaurants. The rebels plan to raise all fabricants to self-awareness and thus disrupt the workforce that keeps the corporate government in power. They want Sonmi to write a series of abolitionist Declarations calling for rebellion. She does, echoing the themes of greed and oppression first brought up in the diary of Adam Ewing.
Sonmi is then arrested in an elaborately filmed government raid and finds herself telling her tale to the archivist. Sonmi believes that everything that happened to her was instigated by the government to encourage the fear and hatred of fabricants by purebloods. Sonmi's last wish is to finish watching Cavendish's story.
The Ghastly Ordeal of Timothy Cavendish (Part 2)
Having mostly recovered from his mild stroke, Cavendish meets a small group of residents also anxious to escape the nursing home: Ernie, Veronica, and the extremely senile Mr. Meeks. Cavendish assists the other residents' conspiracy to trick a fellow patient's grown son, Johns Hotchkiss, into leaving Hotchkiss' car vulnerable to theft. The residents seize the car and escape, stopping at a pub to celebrate their freedom. They are nearly recaptured by Hotchkiss and the staff, but are rescued when Mr. Meeks, in an unprecedented moment of lucidity, exhorts the local drinkers to come to their aid.
It is thereafter revealed that Cavendish's secretary Mrs. Latham blackmailed the gangsters with a video record of their attack upon Cavendish's office; this allows Cavendish to return to his former life in safety. Subsequently, Cavendish obtains the second half of Luisa Rey's story intending to publish it, and he considers having his own recent adventures turned into a film script.
Half-Lives: The First Luisa Rey Mystery (Part 2)
Rey escapes from her sinking car but loses the report, while a plane carrying Isaac is blown up. When her newspaper is bought by a subsidiary of Seaboard, she is fired, and Luisa believes that they no longer see her as a threat. She orders a copy of Robert Frobisher's obscure Cloud Atlas Sextet, which she has read about in his letters to Rufus Sixsmith, and is astonished to find that she recognizes it, even though it is a rarely published piece. However, Bill Smoke the assassin still pursues Luisa and booby-traps a copy of Rufus Sixsmith's report about the power plant. Joe Napier, a security man who knew Luisa's father, and whom Luisa initially believed to be her attempted assassin, comes to her rescue, and Smoke and Napier kill each other in a gun fight. Later, Rey exposes the corrupt corporate leaders to the public. At the end of the story, she receives a package from Sixsmith's niece, which contains the remaining eight letters from Robert Frobisher to Rufus Sixsmith.
Letters from Zedelghem (Part 2)
Frobisher continues to pursue his work with Ayrs while developing his Cloud Atlas Sextet. He finds himself falling in love with Eva, after she confesses a crush on him, though he is still having an affair with her mother. Jocasta suspects this and threatens to destroy his life if he so much as looks at her daughter. Ayrs also becomes bolder with his plagiarism of Frobisher, now demanding he compose full passages, which Ayrs intends to take credit for. Ayrs threatens to blacklist him by claiming he raped Jocasta if he refuses. In despair, Frobisher leaves anyway, but finds a hotel nearby working to finish his Sextet and hoping to be reunited with Eva. He convinces himself that they are being kept apart from her parents, but when he finally manages to talk to her he realizes that the man she was talking about being in love with was her Swiss fiancé. Mentally and physically ill Frobisher ultimately decides, with his magnum opus finished and his life now empty of meaning, to kill himself. Before committing suicide in a bathtub, he writes one last letter to Sixsmith and includes his Sextet and The Pacific Journal of Adam Ewing.
The Pacific Journal of Adam Ewing (Part 2)
Ewing visits the island of Raiatea, where he observes missionaries oppressing the indigenous peoples. On the ship, he falls further ill and realizes at the last minute that Dr. Goose is poisoning him to steal his possessions. He is rescued by Autua and resolves to join the abolitionist movement. In conclusion of his own journal and of the book, Ewing writes that history is governed by the results of vicious and virtuous acts precipitated by belief: wherefore "a purely predatory world shall consume itself" and "The devil take the hindmost until the foremost is the hindmost", and imagines his father-in-law's response to his becoming an abolitionist as a warning that Adam's life would amount to one drop in a limitless ocean. Ewing's proposed reply is: "Yet what is any ocean but a multitude of drops?"
