Ten people are summoned to Indian Island for various reasons by various people. The one common denominator is they are all surprised by the invitation, and the invitations reference either an agency or acquaintance they have had little contact with. They all accept the invitations for different reasons, some to relax with old friends and others to make a little money working in a pleasant environment. What they do not realize is the real reason they have been called to the island.

Dr. Armstrong, Emily Brent, William Blore, Vera Claythorne, Philip Lombard, General John Macarthur, Anthony Marston, Mr. and Mrs. Thomas Rogers, and Mr. Justice Lawrence Wargrave are the sole inhabitants of the island. They each have been involved in one way or another in the death of other people. They each have evaded prosecution for their actions and some of them think their actions were perfectly justifiable.

They all meet for the first time on August 8 as they are being transferred by boat to the island. They discover their hosts are delayed and will not be joining them until the next day, no one has met their hosts, Mr. and Mrs. U.N. Owen. The house staff, which consists of Mr. and Mrs. Rogers, have not met the Owens and have been given their instructions through letters. They and a few of the other guests were contacted by Mr. Isaac Morris, who acted on behalf of Mr. and Mrs. Owen.

After dinner a voice is heard asking for silence from those assembled in the house. The Voice, as it is referred to, reads off charges against each of those present. The Voice accuses each of them of being in some way responsible for the death of others. Most of the guests are horrified, Mrs. Rogers falls into a faint, and they feel the need to explain themselves to the others. Each has a plausible explanation for the death they are accused of, but two feel no remorse for their actions, they are Anthony Marston and Philip Lombard. They feel the deaths of their victims were just happenstance. Mr. Marston killed two children who happened to walk in the path of his car, as he drove too fast down the road. Mr. Lombard was lost in the jungle, so he and his fellow travelers took all the food, leaving their native guides to die. He felt since they were natives they did not mind dying.

The guests wanted to leave the island as soon as possible, but they were told the boat to take them off the island would not arrive until the next morning. Anthony Marston was the only person who wanted to stay and solve the mystery of who made the recording, which is the source of The Voice.

As he declared he wanted to stay, Mr. Marston choked on his drink and died of cyanide poisoning. He was the first to die. Mrs. Rogers was put to bed, because she kept fainting and the doctor gave her a sedative to help her sleep. She never woke up again and this made the others nervous, because they realized they may be next. The Owens had put in each room a framed copy of nursery rhyme which told how ten little Indians met their deaths. The method in which Mr. Marston and Mrs. Rogers died followed the rhyme. On the dining room table is a center piece comprised of ten Indian figures, after each death a figurine mysteriously disappears from the table.

The next morning the boat does not return to the island. Philip Lombard, William Blore, and Dr. Armstrong decide they need to search the island to see if anyone is hiding there, but the search turns up no new information.

After finding General Macarthur dead from a blow to his head, Justice Wargrave tells the survivors the murderer must be one of them. This makes them all look at each other in a new light and raises the anxiety level of the group. They gather all their medicines and possible weapons into one place, all but Mr. Lombard's gun, which is inexplicably missing.

Justice Wargrave is found dead in a chair with a wig made of Miss Brent's yarn and a robe made of a missing bathroom curtain, he has been shot in the head. This coupled with the death of Miss Brent and Mr. Rogers brings the survivors down to five, who spend their time together. They try not to leave each other out of their sight.

During the night, Mr. Blore hears footsteps outside his door and discovers Dr. Armstrong is not in his room. After a search of the island, the three remaining survivors decide the murderer must be Dr. Armstrong, because of this they reason it is safer to leave the house and stay outside. In the meantime, Philip Lombard has found his gun and is keeping it with him at all times. Mr. Blore returned to the house to eat, only to have a bear shaped marble clock dropped on his head. After Mr. Blore's death, during a walk, Philip and Vera find Dr. Armstrong's body on the beach. Philip and Vera are left alone and though an act of self-survival Vera kills Philip. She returns to her room to find a noose and chair waiting for her to hang herself, which she does.

Fred Narracott, takes his boat out to the island and discovers the bodies. After a police investigation, which finds no explanation for all the deaths, a note is found which explains the murders. It was Justice Wargrave who committed all the crimes, because he felt a need to kill and a simultaneous need to provide justice for those he felt were denied it. He also confessed to killing Isaac Morris, by giving him a pill which contained morphine. Justice Wargrave was not killed the first time he was found, but in the end, he killed himself.