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San Hill, leader of the Banking Clan, noticed that Grievous was both a brilliant strategist and an excellent fighter, and asked Grievous to lead the Separatist troops throughout the galaxy against the Republic. Grievous refused, saying that he only cared about the war between the Kaleesh and the Huk, not about the larger conflict between the Separatists and the Republic. Hill brought this to the attention of Count Dooku and Darth Sidious, but despite their offers Grievous still refused to lead the Separatist army.

So Sidious, Dooku, and Hill arranged to have a bomb planted on the shuttle Grievous was on, and to blame it on the Republic. Grievous was mortally wounded in the crash, and his shattered, dying body was taken to the planet Geonosis, where his brain, eyes, and other organs were implanted into a droid body forged by Geonosians that would complement his natural reflexes.

It might have been his rage at the Republic, who he believed caused his shuttle crash; it might have been a feeling of gratitude toward the Separatists for saving his life and giving him a new and improved body; or it might have been the modification that Banking Clan scientists made to his brain while he was unconscious; but when Grievous woke up in his new body he was more than willing to take up Hill's offer and agree to lead the Separatist troops throughout the galaxy against the Republic.

Despite his proficiency with the lightsaber, the general is completely incapable of using the Force.

He first revealed himself to the public when he attacked and dispatched a team of seven Jedi Knights in an aggressive display of lightsaber mastery (which he learned from Count Dooku) during the Battle of Hypori. With his mechanical enhancements and attributes combined, he was able to battle five Jedi single-handedly. Only four survived the onslaught. The Separatist general began the swift conquest of several Outer Rim planets, much to the dismay of the Republic. Time after time, Grievous' ability to strategize attack plans with brilliant ideas and destructive results made the Republic's star fleet commanders shudder at their knees. Grievous himself would later resurface during the Battle of Coruscant, using the first wave of his attack as a distraction to kidnap Chancellor Palpatine. In the process, he killed all the Jedi protecting the Chancellor except Shaak Ti, whose lightsaber he took as an addition to his grisly collection. Grievous was cornered by Obi-Wan Kenobi and Anakin but escaped by smashing a window on the ship and allowing himself to be sucked into space.

The general displays amazing dexterity and is capable of fighting with six lightsabers simultaneously by dividing his mechanical arms into four and holding a 'saber in each prehensile foot while using the repulsorlifts in his legs to float. General Grievous also wears armor made of cortosis, making him resistant to lightsaber attacks. Grievous travels with his droid bodyguards, referred to as "Magnaguards" in Star Wars: Republic Commando for the Xbox, who wield electrified staffs which can defend against most weapons (including lightsabers); they too wear cortosis armour. This is the first time Star Wars fans have seen an non-lightsaber weapon that can withstand the cutting power of a lightsaber itself in a movie. The weakness that Grievous and his bodyguards share is a lack of cortosis on their joint areas, where lightsabers can penetrate.

His movements imitate those of a monkey in his stance and general lightsaber control. Not only can he produce an extra pair of arms, he can use his feet as hands. His "unorthodox" moves mainly involve misdirection with his many limbs, something only the most experienced and talented of Jedi can withstand. Much of this misdirection involves releasing a lightsaber from one limb and catching it with another, sometimes even while two other limbs are performing the same trick. The opponent, focused on limbs which are no longer dangerous, is then struck.

Although General Grievous has no command of the Force whatsoever, he nevertheless has the lightning-quick reflexes and the fighting ability of the Jedi. It is evident that the General has no affinity with the Living Force: this is most obvious when watching him in battle with the Jedi; they cannot feel his presence, only hear and see him.

His only recognized weakness in battle was his inability to take a direct hit from a "Force push" (a phrase coined in the computer game Jedi Knight: Mysteries of the Sith). The Jedi regularly make use of telekinetic abilities. In Grievous's first witnessed encounter with the Jedi (i.e. The Battle of Hypori), the knights attempted to fling objects at him using the Force in order to avoid lightsaber combat. Unfortunately, given the general's superhuman reflexes, this approach proved futile.

He commanded the droid armies of the Separatists under Darth Sidious and Count Dooku. During the Clone Wars, Grievous is continuously hunted by the Republic and the Jedi. He manages to narrowly escape each time.

While on the planet of Utapau, Grievous is ambushed by Obi-Wan. Obi-Wan cuts two lightsabers from Grievous’ arms. Later on in the fight, Obi-Wan loses his lightsaber and physically rips open the general's chest plate so as to expose his heart. He is then able to fire several blaster shots into the revealed vital organs. Grievous crumples to the ground in a flaming heap, dead at last.