"Before the time of the pyramids," a horde from the East invades the ancient world, led by the ruthless Memnon, who by their law, is king for being their greatest warrior. His many victories come from the help of a sorcerer who predicts the outcomes of battles, leaving only a few free tribes to oppose him.
Mathayus, his half-brother Jesup, and friend Rama, the only three true remaining Akkadians, are hired by King Pheron of the last free tribes to kill Memnon's sorcerer for twenty blood rubies, upsetting Pheron's son Takmet, as it is the last of their treasury, and Nubian King Balthazar, who dislikes the Akkadians. The Akkadians manage to sneak into Memnon's camp, but are ambushed by Memnon's guards, having been tipped off by Takmet who killed his own father and defected to Memnon's side. Jesup and Rama are hit by arrows, but Mathayus manages to sneak into the sorcerer's tent, where he sees that the sorcerer is actually a sorceress named Cassandra. Mathayus is then captured and meets Memnon himself, who brutally executes Jesup in front of him, and is about to kill Mathayus too. Cassandra, however, tells Memnon that the gods wish Mathayus to survive the night, and to defy them would incur their wrath and cost him his victories. Memnon has Mathayus buried to his neck in the desert to be devoured by fire ants at dawn, but manages to escape with help from a horse thief, Arpid.
Deciding to finish his mission and avenge his brother, Mathayus sneaks into Memnon's stronghold, Gomorrah, and manages to enter Memnon's palace with help from a street urchin. He briefly meets Memnon's court magician, Philos, who hides him and then directs him to the courtyard where Memnon is training. Mathayus tries to shoot Memnon from the watchtower, but is forced to save the street urchin from having his hand amputated for his theft by shooting the axe out of Takmet's hand, alerting the guards to his presence. Mathayus only barely manages to escape Gomorrah, abducting Cassandra along the way, knowing that Memnon will come for her.
Cassandra tries to escape from Mathayus and even tells him that she has been Memnon's prisoner since she was a child. Sympathetic, Mathayus allows her the choice of leaving, but warns her of worse dangers and that she is likely safer with him. However, Memnon sends his right-hand man Thorak and a group of guards to kill Mathayus and retrieve Cassandra, but Mathayus manages to slay them all under the cover of a sandstorm, while dueling and fatally stabbing Thorak in the abdomen. With his dying breaths, Thorak manages to stab Mathayus in the leg with a scorpion blood-laced arrow. Cassandra, however, uses her magic to save Mathayus's life. As an insult and a warning, Mathayus sends Thorak's blood-stained pendant to Memnon.
Mathayus, Arpid and Cassandra then run into Philos, who earlier fled Memnon's palace and has perfected an explosive powder he was working on. However, they are ambushed by the rebels, now under the rule of Balthazar. Though Mathayus defeats Balthazar in a fight and earns his grudging respect and sanctuary, Cassandra has a vision of Memnon and his army slaughtering the entire rebel camp. She informs Mathayus and then prophesies that when the moonlight reaches the Memnon's palace, the King on High will become the invincible Scorpion King, and Memnon believes himself to be the one destined to become the Scorpion King. Furthermore, she informs Mathayus that if he faces Memnon, he will most likely die. She tells Mathayus that she foresees him being shot, but Mathayus assures her that he will make his own destiny and they make love.
The next morning, however, Cassandra returns to Memnon in order to stall him and possibly kill him. Mathayus, with help from Balthazar, Arpid, Philos and the army of rebels, launches an all-out assault on Memnon's stronghold, facing Memnon personally before he can kill Cassandra, while Balthazar confronts and kills Takmet, avenging Takmet's father, Peron, and takes on the full force of Memnon's forces alone. The battle rages on until Mathayus is shot by a guard as in Cassandra's vision. As Memnon takes his place in the House of Scorpio to become the Scorpion King, Cassandra kills the guard while Mathayus retrieves his bow, pulls the arrow out of his shoulder and uses it to shoot the exhausted Memnon, sending him off the edge of the roof just as Philos and Arpid use the explosive powder to destroy the palace's foundation stone, bringing down the bulk of Memnon's forces. Memnon is consumed by the flames as he falls to his death. With the battle over, the remnants of Memnon's army bow before Mathayus, who, per the laws of the Horde stating that the king is the best warrior, is now the Scorpion King.
In the aftermath, Mathayus and Balthazar share a good-natured farewell as the latter returns to his own kingdom. Cassandra tells Mathayus that she sees a brief period of peace and prosperity coming, but warns him that it will not last forever. Undeterred, Mathayus decides that they will make their own destiny.