Agatha Christie's Cards on the Table is considered to be one of her very best locked room mysteries. Her character, the Belgian detective, Hercule Poirot is invited by Mr. Shaitana to an unusual dinner party. Mr. Shaitana, who chooses to adopt a Mephistophelian appearance, is considered by many who know him to truly be a devil. His favorite occupation is to discover secrets, and then to hold such secrets over those who keep them. The dinner, to which he invites Hercule Poirot, is his way of showcasing his most unusual collection; Mr. Shaitana collects murderers who have gotten away with the crime. Mr. Shaitana considers his hobby to be an amusing one. Hercule Poirot considers the hobby to be a very dangerous one.

On the appointed date, M. Poirot arrives at Mr. Shaitana's flat at eight pm sharp, and is introduced to three other individuals who have arrived prior to Poirot. The three individuals include none other than Mrs. Ariadne Oliver, writer of detective stories, a woman with earnest belief in the capabilities of women. Her most cherished belief is that a woman should be in charge of Scotland Yard. The other two men are Colonel Race, and Superintendent Battle of Scotland Yard. Fifteen minutes later four more people arrive, Shaitana's "collection" of murderers: Dr. Roberts, young Anne Meredith, Mrs. Lorrimore, and Major Despard.

Dinner is delicious, but the conversation turns, predictably, to murder and ways of accomplishing it. Mr. Shaitana specifies his choices of the perfect murder methods, his way of speaking to his four unique guests. After dinner the four guests are taken taken to a room where a bridge table is set up. The other four sleuths, Poirot, Race, Oliver, and Battle are shown to another room where a second bridge table is ready.

Mr. Shaitana claims that bridge is not his game, and he finds it agreeable to sit by the fire as his guests play cards. A couple hours later, the sleuths seek Mr. Shaitana out to thank him for his hospitality. What they discover is a corpse. After ascertaining that no one has entered the room during the time they have been playing cards, suspicion falls on the four suspects. Sometime during the evening, one of Mr. Shaitana's collection has killed their host.

Immediately the four sleuths are drawn into the investigation. Because Poirot has the knowledge that Shaitana believes the four suspects to have previously committed murder, they focus on the suspects' past and the possible murder they may have committed. Each sleuth discovers information that is brought to the table, illuminating the investigation a little, but just not quite enough. At every turn they are stymied and misdirected. With perseverance, they discover the suspicious deaths in Dr. Roberts's past. It is quickly determined that the doctor has probably committed at least one murder and quite possibly more murders in the past. What is lacking is motive for the murder of Mr. Shaitana.

Anne Meredith is young, alone, shy, and dangerous. She has a suspicious murder in her past of a former employer. She chooses to not tell the authorities about that short time in her work history, and her roommate, Rhoda Dawes, is concerned. Rhoda believes in Anne's innocence, but worries that not giving that information will cast unfair suspicion on Anne. This knowledge makes Anne dangerous to Rhoda, who tries to kill Rhoda in order to keep her secret. Major Despard has a death in his past that is quickly determined to have been an accident. Mrs. Lorrimore admits to having killed her husband over twenty years ago, but seems to have no real motive for killing Mr. Shaitana. However, this does not stop her from confessing to the murder, though Poirot refuses to believe her. He discovers the subterfuge in how Mrs. Lorrimore has confessed in order to protect Anne Meredith. Suspicion escalates against Anne when Mrs. Lorrimore is discovered to have committed suicide. Again, Poirot proves that this is really a murder and not a suicide.

The conclusion of the story is Christie's favorite method of a gathering of the remaining living suspects and the revelation of the true murderer. Dr. Roberts is unmasked, having killed Mr. Shaitana in very much the same way he has committed at least three other murders and in the same way he plays bridge. Dr. Roberts has a tendency to overbid his hand both in cards and in his murders. By being very public and open, Dr. Roberts has always been able to make it appear that the deaths were very natural, when in fact they really were murders. Poirot uses his "gray cells" to deduce the character of all suspects, including their bridge playing abilities, to deduce the truth of Mr. Shaitana's murder.