Shortly afterward, and nearly all at once, the Jedi masters leading clone troops were exterminated throughout the galaxy. Clone regiments turned against their Jedi generals and slew them, almost universally to the surprise of the Jedi, e.g. shot from behind either on the ground or in starfighters. Even in the cases when the Jedi realized the situation and tried to defend themselves, they succumbed to the sheer firepower unleashed upon them. Although a Jedi's lightsaber will deflect blaster bolts, the Jedi can not sustain this defense forever, especially against two armies (the droids of the Separatists and the clones of the Republic). Jedi generals leading starfighter and vehicle squadrons were also suddenly targeted and shot down by their clone wingmen or pilots. Among the most notable Jedi killed at the very beginning of the purge were Ki-Adi-Mundi, Aayla Secura, Barriss Offee, Luminara Unduli, Plo Koon, Stass Allie, and Quinlan Vos. Returning to Coruscant, two of the surviving Jedi, Yoda and Obi-Wan Kenobi entered the Jedi Temple long enough to prepare a secret signal with the in-house communications warning all surviving Jedi about the treachery and to take precautions. During this slaughter, Palpatine declared himself emperor.

Following this catastrophic turn of events for the Jedi, Darth Vader was struck down on the fiery Confederate lava homeworld of Mustafar by his former master Obi-Wan Kenobi. Vader was saved by Palpatine and was put into a mechanical suit to keep him alive from the wounds sustained from Kenobi. With this new physical identity, Vader was was given a new task: to hunt down and kill the remaining Jedi scattered throughout the galaxy. Vader traveled from system to system, hunting down and destroying the Jedi until they were all but extinct.