Oxford, England, a brilliant American historian and reluctant witch, Professor Diana Bishop, returns to take up a post at Oxford University. While researching in the Bodleian Library, she unwittingly calls up a magical ancient manuscript, Ashmole 782. Also teaching at Oxford University is acclaimed biochemist and vampire, Matthew Clairmont, who has been looking for this mysterious book, and its explosive secrets for centuries. The appearance of the Ashmole manuscript also comes to the attention of The Congregation's Head Witch, Peter Knox, who is determined to get his hands on it before the vampires do. Frustrated, Matthew confronts Diana to ask her why she is hiding the book and living in denial of her powers. Diana inadvertently triggers Matthew's vampiric instincts and he struggles to control them, leaving Diana mesmerised and terrified in equal measure.

As Matthew fights to control his cravings, he leaves Diana to face her enemies alone. And those include powerful witch Peter Knox (Game of Thrones' Owen Teale).

Still under pressure from the witches, Diana retreats with Matthew to his ancient country home, the Old Lodge, where she discovers his true age. Warming to him she invites Matthew to dinner but the evening ends abruptly when Matthew rejects Diana's advances. Many miles away in Chepstow, the daemon Sophie starts to feel an inexplicable connection with a witch she only knows as the White Queen. She imparts this information to Daemon Congregation member Agatha Wilson. With Matthew's rejection still vivid in her mind Diana retreats to the Library to sort out the issue of Ashmole 782 once and for all. However, Knox is waiting, and his attack on her human friend Sean causes Diana to reveal her elemental powers. After her battle with Knox Diana lies exhausted and exposed, until Matthew comes to her rescue and persuades her to leave Oxford for her own safety.

Diana and Matthew are now guests of Ysabeau De Clairmont, an ancient vampire and killer of witches, at the family's ancestral home, Sept Tours in France. Ysabeau warns Matthew that his love for Diana puts his entire family in danger. Knox is now back at The Congregation and calls an emergency meeting to discuss Matthew's liaison with Diana, as it violates the rule sanctioning relationships amongst species. This puts Baldwin, Matthew's brother and head vampire at The Congregation, on the spot. Later, Domenico, a vampire sent on behalf of The Congregation, turns up unannounced in France to demand Diana's immediate return, and Matthew receives a call that his research lab has been broken into. Fearing Ysabeau was right with her warning, Matthew resolves to abide by the Congregation rules and leaves for Oxford, just as Ysabeau begins to realise how powerful Diana really is.

Matthew crosses a dangerous line when he returns to Oxford. Diana discovers his dark past, before something unexpected tears them apart.

Matthew and his team soon realise Diana's fate and start a desperate search to find her. At La Pierre, Satu conducts a dangerous spell to try to discover the secrets of Diana's magic: it is a terrifying ordeal for the young witch and nearly kills her. Thanks to Em's scrying, Matthew discovers Diana's location and the race is suddenly on to rescue her. Trapped inside a well, Diana is finally able to harness her powers to her own will and flies out of the dungeon before being airlifted to safety by Matthew and Baldwin. Back at Sept Tours, Diana is tended to by Matthew, Ysabeau and Marthe, who discover Satu has left a horrific scar on her. The imprisoned Satu uses magic borrowed from Meridiana, an ancient witch, to free herself,and take Meridiana with her. As enemies begin to appear on several fronts, Matthew calls for Baldwin and the Knights of Lazarus to protect Diana.