In the year 2010, an elderly gentleman named Robert Fowlds discovers a discarded note left behind by a teenage vampire, Eleanor Webb. Intrigued by her words, he invites her into his home, revealing that he is ready to embrace death. In a chilling turn of events, Eleanor kills him to feed on his blood. Meanwhile, Eleanor's mother, Clara, finds herself on the run from her past, having just fled from a lap-dancing club where she worked. In pursuit of Eleanor, a member of the vampiric Brethren named Werner chases her down, ultimately facing the mortal wrath of Clara when she decapitates him and escapes with her daughter.
Seeking refuge, Clara and Eleanor settle in a rundown coastal resort where Clara meets Noel, an unsuspecting man who recently inherited the Byzantium Hotel, a once-bustling establishment now in disrepair. Eleanor captivates those around her by playing the piano at a local restaurant, where she catches the eye of Frank, a young American waiter who expresses interest in her. As Clara seduces Noel and transforms the hotel into a makeshift brothel, Eleanor starts attending college alongside Frank. Curious about her mysterious past, Frank encourages Eleanor to share her story, which she writes down for him, yet he questions the truth of her narrative, ultimately sharing it with their teacher, Kevin.
The film unfolds through a mix of present events and flashbacks to the Napoleonic Wars. Clara's journey begins when she encounters two Royal Navy officers, Captain Ruthven and Midshipman Darvell, ultimately choosing to leave with Ruthven, who subjects her to a life of prostitution following a brutal assault. When Eleanor is born in 1804, Clara, in a moment of despair, leaves her daughter at an orphanage. As time passes, Clara, seemingly ill with tuberculosis, is visited by the vampire Darvell, who provides Ruthven with a map to a mystical island where one can become a vampire if prepared to die. After another confrontation with Ruthven, Clara shoots him and ventures to the island, where she seeks to embrace vampirism.
Upon being accepted into the Brethren, a secret society of predominantly male vampires, Clara's lowly status as a former prostitute draws the ire of its members, yet they spare her life and impose strict codes she must follow. Out of sheer desperation, she secretly visits Eleanor, only to discover that her choices have dire consequences. The villainous Captain Ruthven reappears, dragging Eleanor into a grim fate at the orphanage. Clara intervenes too late, resulting in Eleanor facing a torturous existence. With a mother’s love driving her, Clara decides to turn Eleanor into a vampire, breaking the Brethren's irrevocable rules.
Fast forward to the 21st century, as Eleanor and Frank develop true feelings for each other, prompting her to assist him in becoming a vampire to escape his terminal leukemia. However, complications arise. After learning that Eleanor divulged their history to Frank, Clara is torn between her protective instincts and the restoration of their lives. An unfortunate accident leads to Noel's death, making matters more complex as Clara seeks to shield her daughter from further danger.
The Brethren, relentless in their pursuit, capture Eleanor and take her to an eerie abandoned fairground with the intention of destroying her. In a climactic showdown, Clara confronts them, which leads to a series of tense confrontations. After a fierce battle, Clara faces Savella, the leader of the Brethren, who wields a long-standing grudge against her. In a twist of fate, Darvell, harboring silent feelings for Clara, ends up killing Savella instead of her, allowing Clara to flee alongside Darvell while Eleanor rushes Frank to the island for his transformation.
Thus, the tale of Eleanor and Clara becomes one of love, betrayal, and the ongoing struggle for survival against the dark forces of their world.