Eight strangers are lured to the mysterious Indian Island. Some of them believes that they've been invited by an old friend - one that they can't contact to confirm the invitation. The rest have been hired by a mysterious employer. Once they arrive at the Island they meet the last two 'guests', the husband and wife butler-cook team. In each of their rooms is a poem entitled 'Ten Little Indians' which tells the story of ten Indian boys who die in unusual fashions. A conversation between two of the guests leads them to realize that none of them know their host - the mysterious U. N. Owen. At dinner, they notice ten Indian figurines on the table, matching the poem. After their first dinner, once they're all in the drawing-room, a voice reads out a list of accusations against them - each one of them is accused of murdering at least one person, and they have been brought to the Island to pay for their crimes. No one is sure what to make of the recording, until Marston takes a drink - and dies of Cyanide poisoning. Just as the poem predicted.
Everyone goes to bed uneasy, some feeling guilty about the crimes they've committed, others just worried about their safety. In the morning, they discover that the cook has died in the night as well, although it may have been natural causes... The boat that is supposed to bring supplies is very late, and soon they realize that no one is coming to take them off the Island. They notice, as well, that every time someone dies one of the ten ceramic figurines disappear. As everyone begins to suspect one another, three of the men decide to search the Island to make sure that no one else is hiding on it. After an exhaustive search, they discover that there are definitely only eight people on the Island. For a moment, they believe that the deaths are just a horrible coincidence - until someone turns up with their head smashed in. Since there is no one else on the Island, that means that the killer can only be one of them.
The Judge leads everyone to suspect each other, making sure that everyone understands that no one can be trusted. Everyone goes to sleep scared, some of them slowly being driven mad by their guilt. The next morning, Rogers, the butler, has disappeared. They quickly find his body - he's been murdered with an axe. Everyone starts getting paranoid. Emily, the old woman, begins acting strange, and everyone leaves her alone for a little while - when they return, she's been murdered, leaving only five people left. Wargrave, the Judge, suggests that they lock up all their possible weapons, including the revolver that Lombard brought. The revolver has been stolen though. They tear the house apart looking for it, but they can't find it.
Everyone decides to just sit around, with only one leaving at any one time - theoretically, they should all be safe that way. Vera, the one most wracked by guilt, goes up to her room and is frightened by a strand of seaweed that represents the boy she murdered by drowning. Everyone goes to check on her, and when they return to the drawing room, they discover that the Judge has been murdered - but they can't figure out who had the chance to do it. That night, the ex-policeman, Blore, hears someone sneaking out. He searches the remaining rooms, and discover that Armstrong, the doctor, is missing - so he must be the killer.
The next day, Lombard, Blore and Vera, the three remaining guests, walk around the Island, trying to signal the mainland with a mirror. Blore goes back to the hoe for lunch, but is crushed by a falling slab of marble. Lombard and Vera are sure Armstrong is the murderer - until they find his body washed up against some rocks. Even though evidence has shown that neither of them could be the killer, Lombard and Vera don't trust each other. Vera steals Lombard's gun and shoots him. Happy to finally be safe and alone, and more than a little crazy, Vera walks back to the house, and finds that someone has set up…