The game is told as an autobiography, with an unknown clone recounting the battles of the 501st Legion. The 501st begins as part of the Old Republic, and fights against the Separatists across the galaxy. The campaign begins with Chancellor Palpatine commanding the 501st to destroy an advanced energy generator on Mygeeto, but secretly he wants them to collect the remaining samples to help power his future space station, the Death Star.[8] Meanwhile, Palpatine himself is captured by the Separatists, and the 501st clears the way for Obi-Wan and Anakin Skywalker to rescue him. On Felucia, the 501st exterminates a small infestation of Acklay inhabiting the planet and eventually eliminates the CIS presence in the area. Afterward on the planet Kashyyyk, the clones engage a huge CIS fleet in space, while planetside they defend a vital Wookiee base from a numerically superior enemy army. With the support of Wookiees and Jedi Master Yoda, the invasion is repelled. In the final mission of the Clone Wars era, the clones strike a CIS stronghold on the planet Utapau, killing separatist leader General Grievous, with the help of Obi-Wan Kenobi.
Immediately after the victory on Utapau, Palpatine orders the execution of Order 66. The 501st participate in the destruction of the Jedi Order on Coruscant, and massacre the remaining Jedi knights guarding their temple with the help of the new Sith Lord, Darth Vader.With the newly established Empire in power, the 501st becomes known as Vader's Fist, Darth Vader's personal army. Under their new leader the 501st is assigned to various missions to strengthen the Empire's power. They are first tasked to force a regime change on Naboo by assassinating the Queen and surviving Jedi knights seeking protection. Shortly after, the 501st are called to destroy a droid manufacturing facility on Mustafar that was reactivated by a Geonosian known as Gizor Delso. Learning that the Kaminoans have created a new batch of rogue clones, the 501st is ordered to destroy the cloning facility on Kamino. The 501st battles the altered clone army, gaining victory with the help of the bounty hunter Boba Fett.
With the Galactic Empire firmly established in the ashes of the Old Republic, the 501st receive orders to be stationed on the Death Star. During their watch a prison break is initiated, with crucial plans being stolen by the rebels. Tasked to recover the stolen plans, they search a rebel base on Polis Massa, but the plans are nowhere to be found. The search eventually leads the 501st to the Tantive IV starship. Despite capturing the Rebel sympathizer Princess Leia, the plans are still transmitted, and the Death Star is destroyed with many soldiers still stationed inside. The Empire retaliates by sending the 501st legion to Yavin IV, where a rebel base is located. In the final mission, the 501st is pressed into crushing the weakened Rebel Alliance. The clones defeat the rebels and capture Echo Base, leading to the victory on Hoth. The clone narrator proudly proclaims the Rebellion finished, though the game follows the plot of The Empire Strikes Back, with the Millennium Falcon escaping Hoth