She was trained in the art of thievery by her mother, Dralsi Indoril, and is the granddaughter of Drayven Indoril, who was rumored to be a descendant of the Dunmer saint Indoril Nerevar. She was also involved romantically with Gallus Desidenius, who called her "My Little Nightingale." A former partner in the Thieves Guild with Mercer Frey, Karliah was exiled from the guild for 25 years after he framed her for Gallus' murder.
She is the only Dunmer in the game whose eyes are not red (instead violet) due to her relation with Nocturnal. Her armor is a lighter shade of gray than the Guild Master's Armor Set, and has the same brown-colored straps and satchels of the Thieves Guild Armor.
Once Mercer picks the Dragon Claw door, the Dragonborn walks in first. Karliah shoots the Dragonborn with a poisoned arrow, and the Dragonborn passes out soon after. Awakening again, their vision is blurry. Mercer and Karliah are heard talking. From their dialogue, it is learned that Mercer is guilty of committing many crimes against the Guild. Karliah escapes and Mercer notices the Dragonborn is still alive.
He stabs the Dragonborn, attempting to kill them, but because of the poison on Karliah's arrow, which slowed the Dragonborn's heartbeat and stopped them from bleeding out, they survive. Karliah then takes the Dragonborn back to her camp outside the Sanctum to nurse them. After the Dragonborn regains their strength, the two head to Winterhold to figure out how to decode Gallus' journal.
The Dragonborn is sent to Calcelmo by Enthir to duplicate the writings on the Calcelmo's Stone in Calcelmo's Tower. Calcemo will not let them in so they have to gain entry to his museum in another way.
The Dragonborn learns about the Nightingales and are taken to the Nightingale Hall by Karliah and Brynjolf to become a Nightingale. She wants them to be prepared for the task of killing Mercer Frey for his betrayal.
Karliah and Brynjolf have traveled to Irkngthand in their pursuit of Mercer Frey. They want the Dragonborn to meet them there. Inside they need to locate and eliminate Mercer and take the Skeleton Key he has stolen from Nocturnal.
The Dragonborn must return the Skeleton Key and in order to do so they have to follow the Pilgrim's Path inside the Twilight Sepulcher. After this is done they can go back to the cave and choose a power each day.
- When Karliah appears to teleport or disappear in her confrontation with Mercer, she actually drinks an invisibility potion. It is possible to witness her disguised form leaving.
- Her armour has a dagger strapped on next to the left shoulder.
- She is the only Dunmer in the entire game to have purple eyes instead of the typical red eyes of the Dunmer.
- When asked about the Pilgrim's Path, she says 'it was said they would live forever in twilight' although the subtitles say 'they would become one with the shadows'.
- Karliah has a possible claim to the Septim Dynasty and the Empire's throne, being the daughter of Dralsi Indoril, who in turn was the daughter of Barenziah, the mistress of Tiber Septim . There is no firm evidence of this, however, as Dralsi claimed her father was Drayven Indoril, not Tiber Septim. Barenziah's pregnancies from Tiber and Drayven are about 300 years from each other, meaning that Dralsi would no doubt know if Drayven was her father or not judging by her own age. This makes the chances that she was Tiber's daughter very slim at best, but likely impossible.
- During the quest "Speaking With Silence," if the Dragonborn uses the shout Aura Whisper she will not be detected by the shout like other NPC's.