Over the course of the Clone Wars, Grievous' shrewd battle planning and ruthlessness caused him to become feared throughout the Galactic Republic. The Kaleesh cyborg successfully combated the Republic's Jedi Generals, maintaining a collection of trophies; the lightsabers of Jedi he had slain. He clashed with Padawan Ahsoka Tano and Jedi Master Obi-Wan Kenobi on multiple occasions. Under his command, the droid army wreaked havoc across the galaxy, attacking Kamino, where the Grand Army of the Republic's clone troopers were produced, and wiping out the Nightsisters of Dathomir, and even bombing a crucial power generator on Coruscant, the Republic's capital, to keep the war going during peace talks. Following the reemergence of the fallen Sith Lord Darth Maul, the former apprentice of his master Darth Sidious, Grievous forced his retreat and killed Mother Talzin, the former leader of the Nightsisters.
Near the end of the war, Grievous led the attack on Coruscant aboard his flagship, the Invisible Hand, and successfully captured Supreme Chancellor Palpatine, secretly his master Darth Sidious. However, he was forced to retreat following the death of Count Dooku at the hands of Jedi Knight Anakin Skywalker and the crippling of his flagship, relocating to the remote Outer Rim world of Utapau. Palpatine leaked his location to the Jedi Council, who deployed Master Kenobi to kill the dreaded cyborg. Obi-Wan arrived in Pau City, a miningsettlement in an Utapaun sinkhole, and the Jedi challenged him to a duel, with Kenobi's battalion of clones engaging Grievous' droid forces. Although he attempted to retreat in his personal starfighter, the Soulless One, his Jedi adversary shot the Kaleesh in his organ sack with Grievous' blaster rifle, resulting in the dreaded cyborg's demise.
However the General did not die as Snoke had other plans for Greivous, Intercepting a piece of Greivous DNA Snoke had the General regrown in a secret lab on Sullust. In 6BBY Grievous was fully reborn, at first he nearly attacked Maul but was informed by the latter that the Clone Wars were over. Grievous didn't believe him at first until Snoke emerged from the shadows, Grievous having felt betrayed by Sidious agreed to join Snoke in his anti-Sith cause.