Ten years after the Trade Federation's invasion of Naboo, the Galactic Republic is threatened by a Separatist movement organized by former Jedi Master Count Dooku. Senator Padmé Amidala comes to Coruscant to vote on a plan to create an army of the Republic to assist the Jedi against this threat. Narrowly avoiding an assassination attempt upon arrival, she is placed under the protection of Jedi Knight Obi-Wan Kenobi and his apprentice Anakin Skywalker. The two Jedi thwart another attempt on her life and subdue the assassin, Zam Wesell, a shape-shifter who is killed by her bounty hunter client with a toxic dart before she can reveal his identity. The Jedi Council assigns Obi-Wan to identify and capture the bounty hunter, while Anakin is assigned to escort Padmé back to Naboo, where the two fall in love.
Obi-Wan's investigation leads him to the remote ocean planet Kamino, where he discovers an army of clones is being produced for the Republic, with bounty hunter Jango Fett serving as their genetic template. Obi-Wan deduces Jango to be the bounty hunter he is seeking, and follows him and his clone son Boba to the desert planet Geonosis via a homing beacon placed on their ship, the Slave I. Meanwhile, Anakin becomes troubled by premonitions of his mother Shmi in pain, and travels to Tatooine with Padmé to save her. They meet Owen Lars, Anakin's stepbrother who is the son of Shmi's new husband Cliegg Lars. Cliegg tells Anakin that Shmi was abducted by Tusken Raiders weeks earlier and is most likely dead. Determined to find her, Anakin ventures out and finds the Tusken campsite. He discovers too late that his mother has been tortured by the tribe. As she dies from her wounds, Shmi reunites with Anakin. Anakin kills the Tuskens in his rage and returns to the Lars homestead with Shmi's body. After revealing his deed to Padmé, Anakin says that he wants to prevent death.
On Geonosis, Obi-Wan discovers a Separatist gathering led by Count Dooku, who Obi-Wan learns had authorized Padmé's assassination and is developing a new battle droid army together with Trade Federation Viceroy Nute Gunray. Obi-Wan transmits his findings to Anakin to relay to the Jedi Council, but is captured mid-transmission. With knowledge of the clone army, Supreme Chancellor Palpatine is voted emergency powers to send the clones into battle. Anakin and Padmé journey to Geonosis to rescue Obi-Wan, but are also captured. The three are sentenced to death, but are eventually saved by a battalion of Jedi and clone troopers led by Mace Windu and Yoda; Jango is killed by Mace during the rescue. As the clone and droid armies battle, Obi-Wan and Anakin intercept Dooku and the three engage in a lightsaber battle. Dooku wins, injuring Obi-Wan and severing Anakin's right arm, but then Yoda arrives and engages the Count in a duel. Finding he is unable to defeat Yoda, Dooku flees. Arriving at Coruscant, he delivers blueprints for a superweapon to his Sithmaster, Darth Sidious, who confirms that everything is going well and as planned. As the Jedi gravely acknowledge the beginning of the Clone Wars, Anakin is fitted with a robotic arm and secretly marries Padmé on Naboo, with C-3PO and R2-D2 as their witnesses.
- Diesel 10, Splatter and Dodge, Trixie, and Queen Chrysalis guest star in this film.
- The storyline continues in Thomas and Twilight Sparkle's Adventures of Star Wars Episode III: Revenge of the Sith.