In eighteenth-dynasty Egypt, Sinuhe, a poor orphan, becomes a brilliant physician and with his friend Horemheb is appointed to the service of the new Pharoah. Sinuhe's personal triumphs and tragedies are played against the larger canvas of the turbulent events of the 18th dynasty. As Sinuhe is drawn into court intrigues, and bizarre secrets are revealed to him, he learns the answers to the questions he has sought since his birth. Short on historical accuracy but strong on plot and characterization.

In the 14th Century B.C., in Thebes, Egypt, physician Senmut and his wife adopt a baby found in a basket floating in the Nile River. Although Senmut is one of the few practitioners of brain surgery and could be wealthy, he dedicates himself to the poor, and his values are instilled in his foster son, Sinuhe, who grows up to be a physician. When Sinuhe begins his own practice, he quickly learns that even the poorest people are reluctant to patronize an inexperienced doctor. One day, while roaming the streets looking for patients, Sinuhe meets Kaptah, a loquacious, one-eyed slave who volunteers to be his servant. Then, after failing to save an injured slave, Sinuhe is comforted by Merit, a tavern girl who deeply loves him. Soon after, Pharaoh Amenhotep III dies, and Sinuhe goes out drinking with his best friend, the warlike Horemheb. Horemheb is furious that he has been refused a position with the palace guards because of his lowly birth, and as dawn approaches, persuades Sinuhe to accompany him on a lion hunt. As they pursue a lion, they see a frail young man praying to the rising sun, and Horemheb kills the lion just as it is about to attack him. The man then falls into an epileptic fit, and while Sinuhe tends to him, the palace guard, led by ambitious priest Mikere, arrives and arrests him and Horemheb. When they are taken to the palace, Sinuhe and Horemheb are horrified to discover that the man they helped is the new ruler, Akhnaton. Although Mikere urges Akhnaton to sentence the captives to death for touching him, Akhnaton, who does not believe in treating pharaohs as living gods, refuses. Instead, Akhnaton appoints Sinuhe the court physician and allows Horemheb to join the palace guard. As he is leaving, Sinuhe is questioned by Taia, Akhnaton's mother, and the ambitious Baketamon, his sister. Taia is unusually intrigued by Sinuhe's past, but Sinuhe soon forgets the incident. That night, Horemheb takes Sinuhe to a party at the home of Nefer, a Babylonian courtesan, and Sinuhe is overwhelmed by Nefer's sultry beauty. Although Nefer herself warns Sinuhe to stay away, he becomes obsessed with her and vainly attempts to match the rich gifts given to her by other suitors. As time passes, Sinuhe gives Nefer the necklace given to him by Akhnaton, his medical instruments and house, and even the deeds to his parents' house and their tombs in the City of the Dead. While Kaptah and Merit lament what has happened, Baketamon urges Horemheb to help Sinuhe by pursuing Nefer himself and allowing Sinuhe to find them together. Even proof of Nefer's infidelity does not sway Sinuhe, but eventually, she tires of toying with Sinuhe and banishes him from her home. In a rage, Sinuhe attempts to strangle her, and after Nefer's guards toss him into the street, Sinuhe goes to his parents' home, where he learns that they have committed suicide. Overcome by grief, Sinuhe takes their bodies to the House of Death, where mummies are prepared for the passage to eternal life. Without funds, Sinuhe is forced to work in the abysmal surroundings in order to pay for his parents' embalming, and after ninety days, sneaks their bodies into the City of the Dead, where he intends to bury them. Kaptah tells Merit of Sinuhe's predicament and she follows him into the desert, where she offers him the simple, unconditional love she believes he deserves. The following day, Sinuhe and Kaptah are forced to flee Thebes, as Akhnaton's daughter died while Sinuhe could not be found and the pharaoh has passed a death sentence upon him. Sinuhe and Kaptah spend the next ten years wandering the world, and although he grows increasingly cynical, Sinuhe's fame as a healer spreads and he becomes wealthy. One day, Sinuhe agrees to operate on a Hittite warrior about to lead an army against Egypt, and in exchange for his work, Sinuhe requests the Hittite's sword. Kaptah is puzzled by Sinuhe's bizarre request, then alarmed when Sinuhe returns with him to Thebes, where they are arrested. Sinuhe's motive becomes clear when he gives the sword, made of iron, to Horemheb, now captain of the palace guards, and tells him that without this new metal, the Egyptians will suffer defeat. Horemheb begs Akhnaton to allow him to fight the Hittites, but Akhnaton, whose devotion to Aton, the sun god, has grown, refuses to sanction any bloodshed. Although Horemheb is still devoted to Akhnaton, he tells Sinuhe that the jealous priests of the old gods are tearing apart Egypt in their attempts to bring down the monotheistic pharaoh. Akhnaton forgives Sinuhe for his past mistakes and again appoints him court physician, although Sinuhe turns his back on the poor and treats only the rich. One day, a diseased Nefer comes to Sinuhe for help, and the physician is surprised to find that he no longer desires revenge against her. Feeling renewed, Sinuhe walks through his old neighborhood and runs into Merit and her son Thoth. Sinuhe and Kaptah deduce that Thoth is Sinuhe's son, and the delighted physician promises to start life over with Merit, who has become a follower of Aton. Later, Sinuhe is summoned to the palace, where he learns that the Hittites have invaded Syria and are progressing to Egypt, although Akhnaton continues to refuse Horemheb permission to fight. When Sinuhe examines Akhnaton, his failing health becomes apparent, and the pharaoh, believing that Aton has forsaken him, asks Sinuhe to release him from his pain. Sinuhe demurs and is then confronted by Horemheb and the priests, who ask him to kill Akhnaton so that they will be able to defend Egypt. Sinuhe refuses and laughs bitterly upon discovering that the priests intend to make Horemheb pharaoh after Akhnaton's death. Before he can leave, Sinuhe is summoned by Baketamon, who also asks him to kill Akhnaton and reveals that as the son of one of Amenhotep's other wives, Sinuhe is her half-brother and therefore entitled to rule with her as his consort. Sinuhe is astonished by the news, which Baketamon says was told to her by Taia when he first came to the palace. When Sinuhe sees a statue of Amenhotep in the City of the Dead and recognizes the physical resemblance between them, he realizes she is telling the truth. On their way back to town, they see that Horemheb has begun a massacre of Aton's followers, and Sinuhe rushes to find Merit and Thoth. Sinuhe sends Thoth away with Kaptah, then finds Merit in the Temple of Aton, which is being attacked by soldiers. Sinuhe is unable to save Merit, who is killed by an arrow. Blinded by anger, Sinuhe now agrees to poison Akhnaton, whom he blames for Merit's death because of her belief in Aton. While Akhnaton is dying, however, he praises his god, and his simple belief in a world created in love, in which all men are equal, moves Sinuhe deeply. Sinuhe, who had also intended to poison Horemheb, declares that Horemheb is the pharaoh that Egypt deserves and saves his life. Later, with Baketamon by his side, Horemheb interrogates Sinuhe, who has been arrested for praising Aton and Akhnaton. Horemheb sentences Sinuhe to banishment, and many years later, Sinuhe dies after writing a chronicle of his life in the hope that one day Thoth will find it.