Hellboy, a demonic being who works for the Bureau for Paranormal Research and Defense (BPRD), finds himself caught between the worlds of the supernatural and human as he confronts an ancient sorceress who seeks revenge against humankind. The sorceress, Nimue, known as the Blood Queen, was dismembered centuries ago and her parts scattered across England to prevent her return. In the present day, however, a secret society called the Wild Hunt aims to gather her parts to resurrect her. Hellboy is dispatched to England to assist the BPRD and the Osiris Club in hunting down three giants causing chaos.

Upon arrival, Hellboy learns of the prophecy that he will cause the end of the world. Dealing with feelings of isolation and questions about his own existence, he clashes with people who fear and distrust him, including some within the BPRD itself. Struggling with his identity as a monster prophesied to doom mankind, he grapples with the decision of where his loyalties lie. As Nimue's influence grows and her pieces are brought together, Hellboy encounters a range of characters—from an old acquaintance who's a psychic medium, to a young woman who can speak to the dead, and a merman with valuable information. Together, they must stop Nimue before she regains full power to unleash her vengeance on the world.