Gameplay in Lego Star Wars III: The Clone Wars is similar to the previous titles in the series, and other Lego video games. Up to two players can switch between different characters to fight enemies in combat, solve puzzles, and progress through various levels. It introduces a few novelties, including scene swap, where players can switch between teams in separate locations to complete multi-part objectives, and boss battles. The game also features some real-time strategy elements, such as commanding large ground armies across battlefields. Also, the space fights have been remodelled to use a more instinctive, 3D-space battle sensation. It is set during the Clone Wars animated series, as well as certain scenes from Star Wars: Episode II – Attack of the Clones, unlike the original games, which featured characters from the six films of Star Wars such as Lego Star Wars: The Video Game and Lego Star Wars II: The Original Trilogy. The console version of the game features 115 characters. The portable version features 77 characters. The version for the PSP, 3DS, and DS have some differences from the console version. For example, the ground battles are not featured. The portable version features unlockable minigames like Snowball Fight, Volleyball Droids and more. The rooms where vehicles are also not available to test in the ship itself unlike on the console version. Some levels are removed from the portable version. Some characters such as the Galactic Marine, Chi Cho, Ryo Chuchi, Thi-Sen and others, are featured on the portable version but not on the console version.
Overall, the game engine used by previous Lego Star Wars games has been upgraded. It can now hold more than 200 moving units or objects on-screen. The graphics are more detailed than before, and the lighting has been improved.
New features include scenarios in which players can command large armies of clones to battle against droid armies (although not on DS), and Story Swap mode, in which players can switch between two characters in different areas whose stories run simultaneously. The game includes split screen combat. All new character features include lightsaber throwing, picking up droids and stepping on certain pads in which Jedi do "combo moves" to destroy certain objects. Vehicle levels have been altered; now, players can land their ship and begin fighting on foot (similar to Star Wars: Battlefront II). All the original elements seen in previous Lego Star Wars games have returned. The hub has also been changed, taking place in a Republic Cruiser named the Resolute and also a Separatist Ship the Invisible Hand. Characters can be purchased on these ships- Separatists on the Invisible Hand; characters from the Republic on the Resolute.