Master Thief Garrett is contacted by the Keeper Artemus, who wants him to steal two valuable artifacts. Meanwhile, Garrett learns that the coming of a Dark Age had been prophesied long ago. Gaining access to the Keeper Prophecies, Garrett learns that an ancient book known as the Compendium of Reproach contains more information about the prophecy. As Garrett is trying to solve the mystery, it becomes more and more clear to him that there is a traitor in the order of the Keepers.

Thief: Deadly Shadows is the third installment in the Thief series. The game follows the same design philosophy and gameplay structure that distinguished its predecessors. As before, stealth is the key to successful completion of missions. Avoiding confrontation with the guards, Garrett has to make his way through the levels towards the objective. Shadows and sounds play a large role, as guards will react to suspicious noises, and studying their patrolling routines is essential.

A few gameplay elements have been slightly altered. Garrett can no longer swim, but is able to use climbing gloves that attach him to the walls. He can also flatten himself against walls while standing; if in shadow, he remains completely unnoticeable that way. The player can see Garrett's limbs even if he is viewed from first-person perspective, allowing more precise movements. Switching to third-person view is also possible.

The most significant gameplay change is the non-linear exploration of the City, which has been added to the largely linear missions. In order to access the next mission, Garrett has to explore the City. On his way, he can overhear conversations, steal valuables, avoid or knock out the guards, and even accept secondary missions, which will influence his reputation with some of its factions.