The story begins with eight strangers all on their way to an Indian Island they have been invited to near the coast of England. Some are taking the train and others are travelling by car to the ferry that will bring them to the island. They have all received mysterious invitations for varying reasons, from three people: Mr. and Mrs. U. N. Own and Mrs. Constance Culmington. Vera Claythorne is on her way because she thinks there is a secretarial job waiting for her. Phillip Lombard is simply going because he’s being paid to. Miss Emily Brent and General Macarthur are going because they think they’ve been invited by old friends of theirs. Dr. Armstrong thinks he will be paid to take care of some older women, including the island’s owner’s wife, all of whom are very rich. William Blore is under the assumption he has been hired to spy on the others who will be there because he used to be a detective. Anthony Marston is taking his sports car to the house because he thinks there’s going to be a glamorous party for the rich and famous.
One thing all eight seem to share in common is that on their way to the island, each has a flashback to a prior trauma. They all involve a death in some shape or form. Some are closely connected while others have more distant links with the death. They all get to the ferry and to the captain’s surprise, this isn’t the hip young crowd he was expecting. They arrive at the island and are greeted by Mr. and Mrs. Rogers, servants of the household, who show them to the rooms they will be staying in. What’s strange is that not even they have met the mysterious Mr. and Mrs. Owen yet, because they’d only just been hired. They inform the guests that their hosts will be arriving the next day. Vera Claythorne finds an old piece of paper in her room. The paper has written on it the rhyme “Ten Little Indian Boys.” The rhyme is about the little boys’ actions and eventual deaths.
The guests all go down for dinner, when they begin to get to know one another and get more comfortable around each other and in the home. Afterwards, they are sitting in the drawing room and relaxing while listening to the ocean when they are interrupted by the ear-splitting sound of a voice recording. The voice accuses each one of the guests of unsolved murders in some way. The guests all recount how and why they came to the island. They realize none of them actually knows the hosts. This is when Mr. Justice Wargrave comes to the conclusion that U. N. Owen actually stands for Unknown. He believes that someone mad has invited them to the island to their deaths.
Everyone now starts to explain what really happened with the murders the voice has accused them of. All of them have good explanations as to why they are innocent, although some are very obviously feeling guilty about what happened. Mr. Rogers says that the boat will come back in the morning, so they can leave then. While he’s explaining this, Anthony Marston begins choking on his drink and dies. Scared now, everyone goes up to bed. Mr. Rogers enters the living room to find that one of the ten statuettes present has disappeared. Vera realizes that Anthony’s death is suspiciously similar to the first death in the Ten Little Indians poem she had found.
Some of the guests reflect on the murders they have been accused of. The General knowingly sent the man his wife had been cheating on him with to his death in battle, for one. Vera Claythorne had a child die in her care by drowning. She feels guilty because she had told him he could swim out farther than he could. Dr. Armstrong dreams of his accusation; he had gone ahead with an operation when he was inebriated. He’s awoken from the nightmare by a frantic Mr. Rogers telling him to check on his wife. Dr. Armstrong finds her dead and concludes she was killed by a fatal amount of sleep medication. The guests wake up the next morning hoping to leave but the boat still hasn’t turned up. The oldest person there, the General, is suddenly sure he will never find a way out. He leaves to look at the ocean, but never comes back. Lombard speaks to Dr. Armstrong about what is going on; he thinks they are all here to pay for crimes that cannot be proven in traditional court. Together with Blore, they try to find a way off the island or something else that would save them, but they come up with nothing.
The guests begin to turn on each other and everyone’s motives are brought into question. Dr. Armstrong goes to get the General for lunch and finds him dead from a hit to the head. A storm has been brewing and begins now. They come back to the drawing room to find only 7 figurines remain as they were.
The Judge steps up and tries to figure out logically who the killer is. He doesn’t take anyone out of the running automatically, and they agree that only the ones who have already died can stop being suspects.
Everyone is on edge for the rest of the day and eventually, they all go to bed at night after dinner. Each person locks their door in fear of being killed in their sleep. They wake up the next day to find Mr. Rogers dead. They finally all come to the conclusion that the nursery rhyme is being closely followed in carrying out their deaths.
They eat breakfast and Emily Brent stays back alone at the table for some time because she feels strange. They find her dead from having been injected with poison in her neck. Fearing for their lives, Wargrave starts a search through everyone’s belongings and takes away anything that could be used to kill the others. Those who are left sit together trying to make the time go before they can leave the island. Sick of sitting there looking at everyone like they are the killer, Vera leaves and is planning to take a bath upstairs. She is shocked by some seaweed dangling from the ceiling of her room and the others come rushing to her side thinking she’s being killed next. They return once they realize she’s alright, and find Wargrave to be the next victim. His body is wrapped in a curtain from the house that looks like court robes and with a red mark on his face. The Doctor concludes he was killed by a gunshot to the head.
Very early the following morning Blore wakes up and hears footsteps outside in the hall. Assuming the person missing is the killer, he checks which people are still in their rooms. It turns out Dr. Armstrong is the one not there, so Blore and Lombard go around the island looking for him. After not being able to find him anywhere, they come back to the house and notice another of the figures is missing.
The three people left, Vera, Blore and Lombard, decide that staying out in the open is safest. Blore goes back to get some food and the other two hear a loud crash. Blore was hit with a statue that was thrown from the second floor and he died. They go back to the shoreline and find Armstrong’s dead body; he was drowned. Sure that Lombard must then be the killer, Vera takes his gun and shoots him. She goes back to the house to rest, happy. In her room she sees a noose hanging from the hook she noticed before and gives in to the strange need she feels to hang herself and complete the reenactment of the poem’s last line.
In Scotland Yard, the police are baffled, that is until a confession is found in a bottle. The Judge was the one who did it, he explains he wanted justice for crimes that wouldn’t be given out by the law as it was. What set this off was a doctor telling him he didn’t have long to live, so he decided to go out with a bang, so to say. The confession spells out how he found his victims and how he killed the first five. Then he faked his own death with help from Dr. Armstrong by telling him they would spy on the others together and find the real killer this way. When Armstrong came to see him at the cliffs, the Judge pushed him over the edge and killed him. Now he was able to stay hidden and kill the rest without any of them suspecting him. He watched on extremely satisfied as the rest of the group descended into madness and placed the noose in Vera’s room so she would take her own life.