In 2010, an old man, Robert Fowlds, picks up a discarded note dropped by teenage vampire Eleanor Webb, who has taken to writing her life story and then throwing the individual pages to the wind. Realising what she is, the old man invites Eleanor to his house and tells her that he is ready for death. Eleanor proceeds to kill him and consume his blood. Elsewhere, Eleanor’s mother, Clara, is chased from the lap-dancing club where she has been working. Werner, a member of the vampiric Brethren, demands to know where Eleanor is and captures her after an extended chase. Clara decapitates Werner, burns his body and leaves town with her daughter.

Eleanor and Clara seek sanctuary in a dilapidated coastal resort. There, Clara sets her sights on a lonely soul named Noel, who has just inherited the Byzantium Hotel, a once-thriving business that has fallen into disrepair. Eleanor plays the piano in a restaurant and is approached by a young waiter named Frank, who takes a shine to her. Having seduced Noel, Clara turns the Byzantium into a makeshift brothel and Eleanor joins the local college which Frank also attends. Interested in her past, Frank questions Eleanor, who writes her story for him to read. Not entirely believing it, he shows it to their teacher, Kevin.

The story, revealed in a series of flashbacks over the course of the film, begins during the Napoleonic Wars, when a young Clara encounters two Royal Navy officers, Captain Ruthven and Midshipman Darvell. Much to the dismay of Darvell, Clara leaves with Ruthven, who forces her into prostitution after raping her. When Eleanor is born in 1804, Clara leaves her at a private orphanage. Years later, Clara is dying of what appears to be tuberculosis when the brothel is visited by Darvell, who has become a vampire. He gives Ruthven a map to an island where people can become vampires if they are willing to die. Clara shoots Ruthven in the leg, steals the map and makes her way to the island to become a vampire. Darvell finds Clara and takes her to the Brethren, a secret society of vampires that protects the secret of vampirism.