Padmé Amidala and C-3PO are taken hostage by General Grievous, leaving Anakin and Obi-Wan to save the Senator and complete the destruction of the Malevolence.

Arriving on the desolate ice world of Orto Plutonia, Anakin Skywalker and Obi-Wan Kenobi investigate the disappearance of a clone security force stationed on a remote outpost. The Jedi, accompanied by Senator Riyo Chuchi and Chairman Cho of the nearby moon of Pantora, soon discover their clone troopers were attacked by a tribe of furry natives known as the Talz. Fierce beast-riding warriors, the Talz are very territorial and only want to be left alone. The Jedi manage to negotiate peace with the Talz chieftain, Thi-Sen, when greedy Chairman Cho breaks it by insisting the planet and the Talz are under his power. The resulting conflict escalates into war between the senator led clones and the Talz, with the Jedi in the middle.

The Republic discovers a Separatist bio-weapon lab hidden on the planet of Naboo. Rather than wait for help, Padmé; explores the lab with Jar Jar. Anakin, Ahsoka, Rex, and Obi-Wan arrive and follow after her. They find that the Senator is being held captive by the sinister Dr. Nuvo Vindi. The mad scientist has been developing a lethal virus for the Separatists. Vindi threatens to set off a bomb and release the virus!

In an attempt to force the release of the crime lord Ziro the Hutt from prison, bounty hunters seize control of the Senate Building and hold members of the Senate hostage. Cad Bane, the leader of the operation, with the help of bounty hunter Aurra Sing, issues his demands to Chancellor Palpatine who has no choice but to meet his request. Unbeknownst to the hunters, Jedi Knight Anakin Skywalker is loose in the Senate Building.

The Jedi Council suspects that Senator Rush Clovis, an InterGalactic Banking Clan delegate and former colleague of Padmé Amidala, may be working for the Separatists. Against Anakin's wishes, the Council asks Padmé if she would accompany Rush to Cato Neimoidia to uncover any clues regarding the Senator's true allegiances. Padmé agrees, feeling that her past relationship with the Senator -- which for a time had been romantic until she ended it -- might give her an advantage in the investigation. Fending off Anakin's jealousy, as well as an attempt on her life by Neimoidian Lott Dod, Padmé successfully reveals Clovis to be conspiring with the Separatists to build a military droid factory on Geonosis.

Per Palpatine's order, Republic forces transport a fearsome Zillo Beast back to Coruscant for scientific study. Eager to extract the beast's secrets for military gain, Palpatine orders his lead scientist to examine, and subsequently, kill the monster. Filled with pain and anger, the Zillo Beast escapes from the lab and begins devastating the city. Soon, Anakin, Padmé, and Palpatine find themselves pursued by the beast while the Jedi fight to contain it.

In the middle of a routine shopping trip on Coruscant, C-3PO is abducted by the bounty hunter Cad Bane. Bane is looking for information about the Senate building on behalf of Jabba the Hutt. Finding C-3PO devoid of useful information, Bane and his accomplices kidnap R2-D2 and extract the vital data, before memory-wiping the droids of the incident, and letting them on their way. The floor-plans and security details of the Senate building are part of a plot engineered by the Hutt families to free their imprisoned brother, Ziro the Hutt, who holds potentially damaging information about Hutt activities.

With help from R2-D2 and a squad of captured battle droids, an elite team of Jedi and clone troopers led by Obi-Wan and Anakin attempt to free a captive Jedi general, Even Piell, from an impenetrable prison. Despite orders to the contrary, Ahsoka Tano tags along, though she proves indispensable when the infiltration mission begins to evolve. Piell and his fleet officer, Captain Tarkin, are liberated from their cells, but now the fugitives must escape the Citadel itself.

After groundquakes have devastated the planet Aleen, a Republic relief effort arrives, including the droids R2-D2 and C-3PO. When the native Aleena's pleas go unheard, it becomes the duty of the droids to embark on a surreal journey through Aleen's subterranean world to save the planet.

C-3PO and R2-D2's bizarre caper continues. Forced to escape a Separatist attack in a Y-wing fighter, the droids visit the world of the Patitites, the odd planet Balnab, and the inside of a pirate warship where they are forced to fight in a gladiatorial arena.