Six months after the events of Underworld: Evolution, In 2015 humans have captured Selene during "The Purge", a global military crusade to exterminate vampires and lycans. Vampires have waged guerrilla warfare against the government, but the humans have overrun them, forcing survivors to hide underground and resist the humans on their own.
Twelve years later, human governments have concluded their campaigns against the vampires and lycans. They have annihilated 95% of the vampire race and believe lycans to be extinct. Selene, dubbed "Subject 1", is freed from cryogenic suspension by "Subject 2" and escapes the medical corporation Antigen.
The corporation is ostensibly trying to make an antidote for the virus that creates vampires and lycans. Selene has visions that she follows, believing them to be linked to her lover, the lycan-vampire hybrid Michael Corvin. The visions lead her to a building where she is followed by David, a fellow vampire. While talking with David, Selene has another vision and discovers a young girl, Eve (Subject 2). Eve is revealed to be a hybrid and the daughter of Selene and Michael. Selene and David flee with Eve but are attacked by a group of diseased lycans.
Eve's neck is bitten by a lycan, and David insists that they take her to his coven. David's father, Thomas, blames Selene for provoking the destruction of the vampires. Thomas tells her that Michael died twelve years ago. A vampire doctor examines Eve, offering her blood to help heal. Eve is confused by this, having been raised as human. With Selene's encouragement, she accepts the gift and quickly heals.
