Dungeon Siege III is an action role-playing game set in the medieval fantasy world of Ehb. It has been attacked and defeated by the mysterious Jeyne Kassynder, whose new goal is to destroy everything connected to the Montbarron family, the land's elite guards. The player controls one of four characters (Lucas the fighter, Anjali the fire creature, Katarina the archer, or Reinhart the mage), who have a close connection to this family, aiming to save their lives and uncover the truth behind Kassynder.

The combat system is designed for gamepads, with direct controls for movement and attacks. There are no health or mana potions; instead, characters collect colored spheres dropped by enemies. The player can recruit one of three other characters as a companion controlled by AI, while managing equipment and leveling up choices. Skills include passive talents and active special attacks, which can be specialized in damage or speed.

The game features dialogues with varying outcomes depending on the character used, with choices impacting quest resolutions and story consequences.