On a hot 8 August in the late 1930s, eight people arrive on a small, isolated island off the Devon coast of England. Each has an invitation tailored to his or her personal circumstances, such as an offer of employment or an unexpected late summer holiday. They are met by Thomas and Ethel Rogers, the butler and cook-housekeeper, who state that their hosts, Mr Ulick Norman Owen and his wife Mrs Una Nancy Owen, whom they have not yet met in person, have not arrived, but left instructions, which strikes all the guests as odd.
A framed copy of a nursery rhyme, "Ten Little Niggers" (called "Ten Little Indians" or "Ten Little Soldiers" in later editions), hangs in every guest's room, and ten figurines sit on the dining room table. After supper, a gramophone (or "phonograph") record is played; the recording describes each visitor in turn, accuses each of having committed murder but escaping justice, and then asks if any of "the accused" wishes to offer a defence. All but Anthony Marston and Philip Lombard deny the charges, and Miss Brent refuses to discuss the matter.
They discover that none of them actually knows the Owens, and Justice Wargrave concludes that the name "U.N. Owen" is shorthand for "Unknown". After the recording, Marston finishes his drink and immediately dies from cyanide poisoning. The remaining guests notice that one of the ten figurines is now broken, and the nursery rhyme appears to reflect the manner of death ("One choked his little self and then there were nine").
The next morning, Mrs Rogers' corpse is found in her bed; she had died in her sleep from an overdose of chloral hydrate. By lunchtime, General MacArthur is found dead, from a heavy blow to his head. Two more figurines are found to be broken, and again the deaths parallel the rhyme. Miss Brent relates the account of the gramophone charge against her to Vera Claythorne, who later tells the others.
A search for Mr Owen shows that nobody else is on the island except the remaining seven. The island is a "bare rock" with no hiding places, and no one could have arrived or left; thus, they conclude that any one of the seven remaining persons is the killer. Wargrave leads the group in determining that so far, none of them can definitively be ruled out as the murderer. The next morning, Rogers is found dead while chopping wood, and after breakfast, Miss Brent is found dead in the kitchen, where she had been left alone after complaining of feeling unwell; she had been injected with potassium cyanide via a hypodermic needle.
Wargrave then suggests searching all the rooms, and any potentially dangerous items they can think of are locked up. Lombard's gun is missing from his room. When Vera goes upstairs to take a bath, she is shocked by the touch and smell of seaweed left hanging from the ceiling of her room and screams; the remaining guests rush upstairs to her room. Wargrave, however, is still downstairs. The others find him seated, immobile and crudely dressed up in the attire of a judge. Wargrave is examined briefly by Dr Armstrong and pronounced dead from a gunshot to the forehead.
That night, Lombard appears surprised when he finds his gun returned to his room. Blore catches a glimpse of someone leaving the house but loses the trail. He then discovers Armstrong is absent from his room, and the remaining three guests conclude that Armstrong must be the killer. Vera, Blore, and Lombard decide to stay together at all times. In the morning, they signal SOS to the mainland from outside by using a mirror and sunlight, but receive no reply. Blore then returns to the house for food by himself and is killed by a heavy bear-shaped clock statue that is pushed from Vera's window sill, crushing his skull.
Vera and Lombard are now confident that Armstrong is the killer. However, shortly afterwards, the duo come upon Armstrong's body washed up on the beach. They realize that Armstrong could not have killed Blore. Panicked, each concludes the other must be the killer. Quickly regaining her composure, Vera suggests moving the doctor's body past the shore, but this is a pretext. She lifts Lombard's gun. When Lombard lunges at her to get it back, she shoots him dead.
She returns to the house in a shaken dreamlike state, relieved to be alive. She finds a noose and chair arranged in her room, and a strong smell of the sea. With visions of her former lover Hugo urging her on, she adjusts the noose and kicks the chair out from under her.
Two Scotland Yard officials are puzzled by the identity of U N Owen. Although they can partially reconstruct the deaths from Marston to Wargrave with the help of the victims' diaries and a coroner's careful report, they conclude that U N Owen was one of the victims, but are unable to determine which one. The chair on which Vera stood to hang herself had been set back upright, indicating that someone was still alive on the island after her suicide, presumably the killer.
- Postscript from the Killer
In a postscript, a fishing ship picks up a bottle inside its trawling nets; the bottle contains a written confession of the killings, which is then sent to Scotland Yard. It is not clear how long after the killings the bottle was discovered.
In the confession, Justice Wargrave writes that he has long wished to set an unsolvable puzzle of murder. His victims would be of his choosing, as they were not found guilty in a trial. He explains how he tricked Dr Armstrong into helping him fake his own death under the pretext that it would help the group identify the killer. He also explains that he replaced the chair in Vera's room. Finally, he reveals how he used the gun and some elastic to ensure his own death matched the account in the guests' diaries. Although he wished to create an unsolvable mystery, he acknowledges in the missive a "pitiful human need" for recognition, hence the confession.
He describes how his first victim was Isaac Morris, the sleazy lawyer and drugs trafficker who anonymously purchased the island and arranged the invitations on his behalf, making nine murders and two suicides. Morris was poisoned before Wargrave departed for the island. Wargrave's intention is to stymie the police as to which person on the island was the murderer. He states that, although there are three clues that could guide the police to the correct killer, he is confident they will be unable to find them and that the mystery will remain unsolved until the confession is read.