The opening crawl of Revenge of the Sith explains that Grievous and Count Dooku have kidnapped Chancellor Palpatine and are holding him hostage. Grievous soon has Jedi Obi-Wan Kenobi and Anakin Skywalker captured onboard his vessel, the Invisible Hand. Skywalker and Kenobi escape and confront Grievous on the bridge. Grievous grabs a fallen guard's electrostaff and smashes it through the viewport, sending himself into space. He uses a grappling hook to pull himself to the ship's exterior. He then uses his mechanical feet to magnetize to the outside of his fallen flagship to regain entry into the vessel, and flees in an escape pod.
Grievous directs his escape pod to the nearest Trade Federation control ship, where he orders his armies to retreat. He then travels to the planet Utapau, where the Separatist Council reside. Grievous is now the supreme leader of the Confederacy, as Dooku, the previous leader, died at Skywalker's hand in the earlier battle. Sidious orders him to move the Separatist leaders to the volcanic planet Mustafar.
Kenobi arrives shortly after the Separatists leave, and corners Grievous, who engages Kenobi in combat. Kenobi seems to gain the upper hand, fending off Grievous' lightsabers and slicing off his two lower hands at the wrists; Grievous, however, escapes on his four-legged/single wheeled vehicle as the elite Republic assault force known as the 212th Assault Battalion begins its attack on the droid armies. Kenobi, atop his steed Boga, chases after Grievous throughout most of the battlefield, and due to a blast from his own Clone Troopers, drops his lightsaber. He eventually pulls alongside Grievous and leaps to the general's vehicle, which soon careens out of control due to the intense struggle between him and Kenobi. Grievous and Kenobi fall from the craft to the surface of Grievous' secret landing platform, where he has his fighter docked. Grievous tries to shoot Obi-Wan, but Kenobi knocks the blaster away with Grievous' electrostaff. They begin to fight hand to hand, since the only weapon between the two of them is an electrostaff Grievous had on his vehicle. Kenobi rips open Grievous' chest-plates, revealing his internal organs. Grievous swings him around violently before hurling him over the edge of the landing platform and seizing the electrostaff to finish the job.