The novel begins with a brief explanation—provided by its narrator, Arthur Hastings—of why it's being written. Hastings alludes to a sensational crime that took place at Styles Court and has dominated the regional news cycle for an entire summer, and he claims to have been asked by the Cavendish family, the proprietors of the estate, to write a true account of the whole affair to dispel any lingering rumors. So, Hastings recounts the summer he spent at Styles after being injured in WWI and recuperating in a convalescent home. At some point between his stay at the convalescent home and his two months of leave, Hastings runs into John Cavendish, an old acquaintance. John catches Hastings up on his family drama—John's stepmother, Emily, has married again, this time to a man twenty years her junior. John is sure that the man is a scoundrel, only in it for the money. In the course of their conversation, John invites Hastings to stay at Styles for the duration of his leave, and Hastings takes him up on the offer.
Once he arrives at Styles, Hastings is immediately taken with John's wife, Mary, to whom he confesses he has always wanted to be a detective. Hastings meets John's brother, Lawrence, a physician by training, but not in practice. Lawrence instead spends his time and family's money writing and publishing poems, which John says are not very good. He meets Cynthia, who works at the hospital dispensary compounding medicines; Evelyn Howard, a senior member of the staff at Styles, who also works at a hospital and is a close, longtime friend of Emily Ingethorp's; Alfred Inglethorp, Eve's distant cousin, an employee of one of Emily's foundations, and, as of recently, Emily's new husband; and Dorcas, Emily's loyal maidservant. And, of course, Hastings sees Emily, whom he hasn't seen in a very long time. He observes Alfred to be attentive, almost obsequious, regarding his wife.
Early on in Hastings' stay, tragedy strikes. In the middle of the night, a commotion is heard coming from Emily's room. Her door is latched, so Lawrence, John, and Hastings all work together to break it down. When they get into the room, they see Emily convulsing; shortly, she is dead. Their neighbor, a German doctor by the name of Bauerstein, who also happens to be a foremost expert on poisons and toxicology, is nearby and quick to the scene. Following Bauerstein, Emily's personal doctor, Dr. Watkins, arrives. Both doctors determine that they cannot sign off on a death certificate that cites natural causes before a post-mortem is done, and they strongly suggest keeping the bedroom door bolted so no one can interfere or tamper with the scene. Essentially, they suspect foul play.
Enter Hercule Poirot, a retired detective who happens to be staying at a boardinghouse in Styles St. Mary courtesy of Emily Inglethorp, who tried to use her wealth to relieve suffering during the War. She put up a group of Belgian refugees in town, and Poirot is among them. Hastings met Poirot while he was abroad fighting in WWI, and when he runs into him, he immediately recruits him to investigate the curious circumstances of Emily's death.
The primary suspect from the beginning is Alfred Inglethorp, who everyone already thought was suspicious and only in the marriage for the money. Alfred stands to gain the most now that Emily is gone, seeing as their marriage makes him the primary beneficiary of her will. Evelyn Howard, Emily's friend, who was staying at Styles until shortly before her death, hates Alfred and makes a show of denouncing him as often as she can. In fact, the reason she wasn't staying at Styles the night of the tragedy is because she confronted Emily about Alfred. She warned her that he would kill her in her sleep to get his hands on her fortune. Howard returns to the estate after news of Emily's death reaches her. She immediately blames Alfred and can't understand why anyone would think he wasn't the guilty party.
There is an inquest, and Alfred is quickly charged with murder after failing to provide an alibi for the night of the murder and refusing to answer the prosecutor's questions. Poirot, however, doesn't think it is wise to actually arrest Alfred, so he takes his theory to Scotland Yard. Poirot suspects that, for some reason, Alfred actually wants to be arrested, since he has such an ironclad alibi that he is refusing to disclose at the inquest. Poirot shares his information with Detective-Inspector Japp, thus clearing Inglethorp and proving that he could not have been the one to purchase strychnine from the chemists at that time, on the day the strychnine was purchased, the transaction of which was documented and signed for on a ledger, apparently by an imposter.
Christie takes the reader through the paces, and almost every major character is at one point a prime suspect. Mary is proven to have drugged Cynthia and Emily in order to steal a letter from Emily's room on the night of her death, but the draught Emily gives her was not the killing draught. Cynthia's intimate knowledge of bromides and poisons and the fact that she's the one to prepare Emily's medicine makes her another prime suspect. Then, of course, both Cavendish brothers are suspects; John is actually charged and put on trial, and even spends two months in jail until he is ultimately cleared when Poirot proves that it was Alfred Inglethorp and Evelyn Howard who murdered Emily in order to inherit her fortune and spend the rest of their days together in retirement. Alfred was so eager to get himself charged the first time so that he could later demonstrate his alibi, clear his name, and by the rule of double jeopardy, not be charged again for the same crime.
Throughout the novel, Hastings has a handful of personal crises of his own. For one, he is enamored of Mary Cavendish, but she is wholly unattracted to him. She is having an affair with Dr. Bauerstein but is, after all, still in love with her husband John (who is also having an affair with Mrs. Raikes, the neighboring farmer's wife). Hastings also at one point asks Cynthia to marry him, and she laughs his proposal off. Cynthia and Lawrence end up together in the end. Hastings' most persistent crisis is the way he feels he is undervalued by his friend Hercule Poirot. Hastings feels out-of-the-loop the whole time, always several steps behind Poirot. He feels like a pawn in Poirot's masterplan. But in the end, it is clear that Poirot enjoys working with Hastings and plans to work with him again on future cases.