In the Dark Ages, the Blood Queen Nimue (Milla Jovovich) (A powerful and ancient medieval British sorceress who seeks to destroy mankind) unleashes a plague on England until King Arthur (Mark Stanley) stops her with the aid of Ganeida (Penelope Mitchell) (An elder witch who has decided that Nimue's wrath has gone on for too long and must be stopped), a member of her coven. Arthur uses Excalibur to dismember Nimue, and hides her remains across England.In present day Tijuana, Mexico, paranormal investigator Hellboy (David Harbour) (An immensely powerful Cambion who works for the government organization Bureau for Paranormal Research and Defense (B.P.R.D.)) reluctantly kills missing Bureau for Paranormal Research and Defense (B.P.R.D.) agent Esteban Ruiz, whose mission got him turned into a vampire. After hearing Ruiz's dying words that the end is coming, Hellboy is brought back to the B.P.R.D. in Colorado. He is assigned by B.P.R.D. leader Trevor Bruttenholm (Ian McShane), his adoptive human father, to assist in the Osiris Club, a secret society that studies the occult, in their hunt for three giants. Hellboy is informed by the club's seer Lady Hatton (Sophie Okonedo) that Bruttenholm was meant to kill him when he first came into the world as the result of the Nazis' Project Ragnarok back in 1945 (Hellboy was working for the Nazis when he summoned Hellboy, but was killed by allied forces once the ceremony was completed. Bruttenholm was part of the allied party who rescued Hellboy and decided to convert him into a force of good). Meanwhile, the hog-like fairy Gruagach (Stephen Graham and Douglas Tait) (A hog-like fairy who restored Nimue to exact revenge on Hellboy) retrieves several of Nimue's remains.During the hunt, Hellboy is betrayed and nearly killed by the Osiris hunters (the giants were a ruse to lure Hellboy to UK. In reality the Osiris club recognized Helloby as the "end of the world" threat to humans and wanted to kill him before he could turn on them) before they are ambushed by the giants. Barely conscious, Hellboy manages to defeat the giants before being rescued by a young woman. Hellboy awakens in the woman's flat and recognizes her as Alice Monaghan (Sasha Lane) (who retained some magical abilities after she was kidnapped by fairies as a baby), a medium he once rescued from fairies as a baby. Sending a SWAT team to retrieve Hellboy, Bruttenholm relays that someone has taken Nimue's remains and is seeking the last piece at the Osiris Club. They are introduced to M11 agent Ben Daimio (Daniel Dae Kim) (A rugged Japanese-American military member of the B.P.R.D. who, due to a supernatural encounter, can turn into a jaguar when angered or in pain), and Hellboy and Alice join the team headed to the club. Finding everyone at the club slaughtered, Alice channels Hatton's spirit, who reveals that Nimue seeks Hellboy to cause the apocalypse. Nimue's arm is taken by Gruagach, and Nimue distracts Hellboy by appealing to his frustrations, allowing Gruagach to escape. Hellboy reveals that Gruagach is a changeling who took baby Alice's place before Hellboy branded him with iron. Gruagach, with the guidance of witch Baba Yaga (Emma Tate and Troy James), revives Nimue to exact revenge on Hellboy for ruining his chance of being human.Daimio takes them to M11 headquarters before secretly acquiring a special bullet to kill Hellboy. After an argument with Bruttenholm about his adoption (Hellboy is not convinced why Bruttenholm kills every monster that walks the earth and yet decided to spare his life when he had the chance. He wants a world where monsters can live peacefully), Hellboy leaves before being magically transported to Baba Yaga's house. Having shot out Baba Yaga's right eye, Hellboy is talked into giving up one of his eyes for the location where Nimue plans to restore herself. Hellboy reneges on the agreement, and Baba Yaga curses him. On the way to Nimue's location in Pendleton, Daimio reveals to Alice that he was the sole survivor of a were-jaguar attack.The group arrives after Nimue's full resurrection, and kills her coven with the exception of Ganeida. Nimue poisons Alice and flees with Gruagach; Ganeida directs Hellboy to the resting place of the wizard Merlin (Brian Gleeson) to save Alice. Hellboy and Daimio excavate Merlin's still-living body, and Merlin cures Alice before putting her and Daimio to sleep. Merlin tells Hellboy that he is descendant of King Arthur through his mother who was spirited to Hell by his father. When offered Excalibur, Hellboy refuses it after a vision of himself causing the apocalypse. Merlin, having exhausted his magic, disintegrates.The trio return to London to find the M11 staff dead and Bruttenholm missing. They follow Nimue to St Paul's Cathedral, and Hellboy fights an empowered Gruagach aided by Daimio in were-jaguar form. Nimue kills Gruagach, and knocks Hellboy into Arthur's hidden tomb that holds Excalibur. Hellboy initially refuses to pull the sword, but reneges when Nimue kills Bruttenholm. The sword's removal opens a portal to Hell from which demons emerge and attack London. Alice channels Bruttenholm's spirit to dissuade Hellboy and he decapitates Nimue, throwing her head into the closing portal after the demons are sent back to hell. Hellboy and Bruttenholm exchange farewells, and Daimio discards the special bullet.Six months later, the trio raid a cult club where they find the water tank of an Ichthyo sapiens. In a mid-credits scene, Hellboy is consoled at Bruttenholm's grave by the ghost of his hero Lobster Johnson (Thomas Haden Church). In a post-credits scene, Baba Yaga enlists an unseen force to seek out Hellboy with the promise of allowing him to finally die.