Beautiful twenty-year-old Linnet Ridgeway is one of the wealthiest women in England, the heir to a vast fortune. She is in the final stages of renovating her newly-acquired estate, Wode Hall, when her best friend, the poor but clever Jacqueline “Jackie” de Bellefort asks a favor: could Linnet hire Jackie’s fiancé, Simon Doyle, who is penniless and recently out of a job? Linnet agrees to meet Simon and is immediately drawn to him. Soon the handsome, charming Simon is not only her land agent but also her husband.

Linnet and Simon depart for their honeymoon. Linnet is apparently one of the luckiest women on earth: she’s young, healthy, fabulously wealthy, enchantingly beautiful, breathtakingly glamorous, newly in love, and blissfully happy. But what seems like the beginning of a charmed life is actually the beginning of the end. First, Jackie enacts a form of psychological revenge that leaves Linnet desperate and shaken: everywhere Linnet and Simon go on their honeymoon, they find Jackie there, too.

Tensions heighten as Simon and Linnet embark on a Nile cruise. Their fellow passengers bring their own share of mysteries and intrigue on board the Karnak with them: there’s the quiet Mr. Fanthorp, whose claims to be on holiday are unconvincing; the radical Mr. Ferguson, consumed by resentment toward the upper classes; Linnet’s uncle, Andrew Pennington, who claims to have encountered her abroad by mere coincidence (but whose luggage tags suggest another story); Mrs. Otterbourne, a novelist in decline, harboring an unnamed illness; and her daughter Rosalie, who seems to suffer some inner torture. There’s also the pleasant Mrs. Allerton, whose son, Tim, is inexplicably wary of questions about his relationship with his cousin, Joanna; the cunning and mysterious maid, Louise, newly in Linnet’s service; Richetti, the archaeologist desperate to keep the contents of his telegrams private; and the snobbish old Miss Van Schuyler, whose constant demands terrorize her sweet niece, Cornelia, who seems to have something to hide. Luckily, the renowned detective, Hercule Poirot, is also on board.

Linnet expresses growing unease, claiming to feel the hatred of all those around her. One day, on a sightseeing trip ashore, a boulder comes hurtling toward Linnet. This is the first attempt on her life (or is it just an accident?).

One night, after a particularly stifling day, tensions come to a head. Jackie has too much to drink in the saloon and seems bent on provoking Simon, and telling the world how he has wronged her. She loses her temper, draws her pistol, and shoots. In the flurry of activity that follows, Simon, who has not been mortally wounded, gets care, while a morbidly-repentant Jackie, seemingly bent on suicide, has her pistol goes missing.

The next morning, Poirot and his friend, Colonel Race, awaken to a second jolt of grim news: during the night, Linnet was shot dead, the killer’s modus operandi identical in every respect to the murderous fantasy Jackie once confessed to Poirot. Jackie is the only person on the Karnak with a pearl-handled pistol, ample motive, and a professed intent to kill Linnet, but there’s just one catch: Jackie, who was drugged and under the close watch of a nurse all night, couldn’t have done it.

Poirot begins a search for the murderer but before finding him or her, he uncovers the other passengers’ lies and secrets: Rosalie Otterbourne’s reason for throwing a parcel overboard on the night of the murder; what became of Linnet’s costly pearls; Tim and Joanna’s secret; the dark truth about Mrs. Otterbourne’s illness; and the true motivation for Fanthorp’s trip abroad, not to mention the identity of a dangerous agitator and known killer who turns out to be on board.

As Poirot gets closer to the truth, two more passengers lose their lives: Louise Bourget, Linnet’s maid, who appears to have tried to blackmail the killer; and Mrs. Otterbourne, whose secret dealings with the ship’s crew put her in the wrong place at the wrong time.

With Race’s help, Poirot unravels the interlocking mysteries and brings the killers to an imperfect but humane justice.