There are several passengers on a train, en route to the mysterious Indian Island: Justice Wargrave, Vera Claythorne, Philip Lombard, and Emily Brent. General Macarthur, another invitee to the island, is on a different train, while Dr. Armstrong drives to the island, as well as Tony Marston. Finally, Mr. Blore, a former detective and another guest, is on a different train.
Once the group arrives at the house on Indian Island, they are told by the butler, Mr. Rogers, that the host Mr. Owen has been delayed, at which point the guests settle into their appointed rooms.
After dinner, the guests move into the drawing room, when a voice accuses each of the guests of murder. Rogers admits to turning on the record player, but he says he was only doing what he was told by Mr. Owen, whom he admits he never met. The guests realize that “Mr. Owen” impersonated the guests’ various old friends in the invitation each guest received. Wargrave suggests that a homicidal maniac has invited them to the island.
The guests defend themselves against the accusations, each insisting that they are not responsible for a murder. They all agree with Wargrave that they should leave in the morning, except for Marston who suggests that they stay and solve the case, but when he goes to sip his drink, he chokes and dies.
After discovering that Marston’s drink was poisoned, the guests return to their rooms, where Wargrave thinks about Edward Seton, the man whom the voice accused him of sentencing to death. Downstairs, Rogers notices that there are now only nine statues on the table, whereas before there were ten.
Rogers, worried that his wife is not waking up, awakens Armstrong who finds that Mrs. Rogers has died in her sleep. In the morning, Vera, Lombard, and Blore wait for the boat back to the mainland, but it does not arrive. The group learns that Mrs. Rogers died, and they begin to speculate on the cause of her death. Rogers shows Armstrong that only eight statues remain on the table.
Emily and Vera take a walk, and Emily reiterates her belief that Mrs. Rogers died of a guilty conscience. Lombard and Armstrong discuss the possibility that Rogers killed his wife and that the couple might have been responsible for the murder they were accused of. They conclude that Mr. Owen must be the one committing the murders and is hiding on the island.
Blore, Armstrong, and Lombard search the island for Mr. Owen when they come across a cliff with caves underneath. Unable to reach it without a rope, Blore returns to the house to get one. Vera comes across Macarthur who talks of the impending end of his life. Blore, Armstrong, and Lombard search the caves but do not find any evidence that Mr. Owen is hiding there.
Blore argues with Armstrong over the possibility that he was responsible for Mrs. Rogers overdose as he was the one that provided her with sleeping medication. Blore also questions Lombard as to why he carries a gun, which Lombard explains he brought as a precaution. The guests discover that Macarthur was killed, and that only seven statues remain on the table. Wargrave leads a meeting with the remaining guests in which he concludes that the murderer must be one of them.
After dinner, the guests retire to their rooms, locking their doors, and Rogers locks the dining-room door so that no one can remove any more of the statues during the night.
The next morning, Vera discovers that another statue has gone missing and, later, Rogers’s body is found, which causes Vera to suffer a breakdown. The remaining guests behave politely, but frantic thoughts flood their minds.
They find Emily dead, apparently having died from a syringe injection. Wargrave suggests they lock away any potential weapons including Lombard’s gun, but when they go to his room to retrieve it, they find it is missing. The guests store all potentially lethal drugs in a case that requires a key and place it in a chest that requires a different key. Wargrave gives one key to Lombard and one to Blore.
The group sits nervously in the drawing room where they decide that only one person will go anywhere at a time. Vera gets up to take a shower when she feels something touch her throat and screams, causing the group to rush to her room to find a piece of seaweed hanging from the ceiling. The group notices that Wargrave is not with them, rush downstairs, and find his dead body sitting in a chair.
Lombard finds that his gun is back in its drawer. Blore goes over the facts of the case in his head when he hears a noise. When Blore goes to investigate, he finds that Armstrong is not in his room, and he wakes up Lombard and Vera to help him search, only to find that only three statues remain.
Vera, Blore, and Lombard attempt to signal the mainland but receive no answer, and they decide to stay outside to avoid the danger of the house. Blore, however, returns to the house to find something to eat, leaving Lombard and Vera alone. They hear a crash and find Blore crushed to death by a clock.
Vera and Lombard find Armstrong’s body on the beach. Vera points Lombard’s revolver on him, at which point Lombard lunges toward her only to be shot dead. Vera returns home and thinks of Hugo, the man she loved, and goes upstairs where she finds a noose hanging from a hook, and she decides to hang herself.
The police arrive and discuss the unusual events that took place on the island. The rest of the epilogue follows a manuscript written by Wargrave that reveals himself as the killer, his motive for killing the guests, and how he carried out his plan.