American notary Adam Ewing witnesses the enslavement and near-extinction of the Moriori people on the Chatham Islands, begins a sea voyage home, befriends a Moriori stowaway named Autua, and places his trust in the sinister Dr. Henry Goose. The diary breaks off mid-sentence.

In 1931 Belgium, penniless English composer Robert Frobisher finds half of Ewing's diary, becomes amanuensis to the aging Vyvyan Ayrs, falls into a predatory working relationship with him, begins composing the Cloud Atlas Sextet, and writes letters describing his growing entrapment to his lover Rufus Sixsmith. The letters break off before the end.

In 1975 California, journalist Luisa Rey meets an elderly Rufus Sixsmith, who has damning evidence that a nuclear reactor is dangerously flawed. Sixsmith is killed before he can pass her the report. Luisa pursues the story against corporate assassins, a planted car bomb, and a cover-up that goes to the top of Seaboard Power. The narrative breaks off before resolution.

London vanity press publisher Timothy Cavendish accidentally makes a fortune on a gangster's prison memoir, refuses to share profits, is threatened by the gangster's brothers, and flees — only to be committed involuntarily to a nursing home in Hull by his own brother. He is trapped. The narrative breaks off before his escape.

In a near-future corporate dystopian Korea called Nea So Copros, Sonmi~451 — a genetically engineered 'fabricant' designed to serve fast food — achieves consciousness after exposure to banned literature and a rebellious colleague. She is extracted by the underground resistance. Before her execution, she gives a recorded interview — the Orison — describing her journey from servitude to consciousness to revolutionary icon. The interview is the narrative.

Far-future Hawaii, after the Fall has ended industrial civilization. Zachry, a member of the Valleysmen tribe, lives in a world that has returned to subsistence farming and oral tradition. A Prescient woman named Meronym arrives to find a communications relay. Zachry is haunted by a devil figure called Old Georgie, who represents the predatory impulse. Meronym and Zachry recover the relay. They leave the island as the savage Kona tribe destroys the Valleysmen. Zachry tells this story to his grandchildren around a fire.

The novel collapses backward through the second halves of all five preceding narratives. Sonmi is executed after revealing she always knew she was a managed martyr. Cavendish escapes Aurora House in a geriatric jailbreak. Luisa publishes the nuclear exposé. Frobisher completes the Sextet and shoots himself. Ewing survives Goose's poisoning, is saved by Autua, and resolves to join the abolitionist cause. Each ending radiates back to inform the earlier, interrupted reading.

An analytical overview of Mitchell's nested narrative structure, the comet birthmark as reincarnation device, the chain of artifact and encounter that connects each story, and the way the novel's form argues its content.