Clone troopers continued to serve as the main infantry units throughout the Clone Wars, participating in most battles throughout the galaxy-wide war. While most clones were standard infantry, some took on specilist roles, such as , , and , however all had some degree of proficiency with handheld blaster weapons. Clone trooper armour evolved over the course of the three-year war, first beginning with the Phase I armour, and transitioning into Phase II, which was more confortable for the troopers to wear and offered greater protection.
As the Clone Wars drew to a close, Chancellor , who was secretly the Sith Lord Darth Sidious and enemy to the Jedi, ordered the clone troopers to execute Order 66, designating the Jedi as traitors to the Republic who should be shot on sight. The vast majority of clones complied, killing their former Generals and crippling the Jedi Order. After Palpatine reformed the Republic into the Galactic Empire and declared himself Emperor, he ordered his apprentice, , formerly the Jedi Knight to eliminate the Separatist leaders who he knew were stationed on the planet Mustafar. After Vader completed this task, he then broadcast a signal he obtained from the Separatist base, which shut down the droid forces, effectively ending the Clone Wars.
Shortly afterward, Sifo-Dyas was by the at the behest of the , consequently resulting in the Sith's takeover of the clone trooper project. , the of the , recruited the to become the of the clone army. Various modifications were made to the Fett so that the clones would grow faster and be more susceptible to following orders. The Kaminoans resorted to growth acceleration in order to create mature clones in half of the time that it took for a normal to reach maturity; Fett's genetic structure was further modified to make the clones less independent and more docile than their template. However, the clones were also designed to be capable of creative thinking, making them superior to (according to the Kaminoan ). Of the multitudes of clones, Fett requested that one remained unaltered, so that he could adopt the boy as .