Planescape: Torment's protagonist is "The Nameless One," an immortal being who, if killed, will wake up later, sometimes with complete amnesia. Each time The Nameless One dies, another person in the multiverse dies to fuel his resurrection. These dead turn into ghosts that seek revenge on him. When the game starts, The Nameless One wakes in a mortuary with no memories, as a result of his latest death. He sets out on a quest to regain his lost memories and discover why he is immortal. He slowly learns about the personalities of his previous incarnations, and the influence they have had on the world and people that surround him.

Over the course of the game, The Nameless One meets seven characters who can join him on his quest: Morte, Annah-of-the-Shadows, Dak'kon, Ignus, Nordom, Fall-From-Grace, and Vhailor. These playable characters can also interact with the Nameless One to further the game's plot. Morte is a cynical floating skull originally from the Pillar of Skulls in Baator. He is introduced at the game's beginning in the mortuary. Morte loyally follows The Nameless One, partly out of guilt for having caused the deaths of some of his previous incarnations. The Nameless One meets Annah-of-the-Shadows, a young and brash tiefling (a human with fiendish ancestry) rogue, outside the mortuary, but she does not join the group until a later point in the game. Dak'kon is a githzerai, who once made an oath to follow The Nameless One until the latter died, not knowing of The Nameless One's immortality; this bound him to The Nameless One for eternity. Ignus is a pyromaniacal mage who was the apprentice of one of The Nameless One's past selves. In the Rubikon Dungeon Construct, the Nameless One can find Nordom, a modron disconnected from its species' hive mind. Fall-From-Grace is a succubus who acts as proprietress of the Brothel of Slaking Intellectual Lusts in Sigil; unlike other succubi, she is not interested in seducing mortals. Vhailor, found below the city of Curst on the plane of the Outlands, is essentially an animated suit of armor dedicated to serving merciless justice.

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