In the final days of World War II, the Nazis attempt to use black magic to aid their dying cause. The Allies raid the camp where the ceremony is taking place, but not before they summon a baby demon who is rescued by Allied forces and dubbed "Hellboy". Sixty years later, Hellboy serves the cause of good rather than evil as an agent in the Bureau of Paranormal Research & Defense, along with Abe Sapien - a merman with psychic powers, and Liz Sherman - a woman with pyrokinesis, protecting America against dark forces.

For more than a decade, parents Andy and Vicky have been on the run, desperate to hide their daughter Charlie from a shadowy federal agency that wants to harness her unprecedented gift for creating fire into a weapon of mass destruction. Andy has taught Charlie how to defuse her power, which is triggered by anger or pain. But as Charlie turns 11, the fire becomes harder and harder to control. After an incident reveals the family's location, a mysterious operative is deployed to hunt down the family and seize Charlie once and for all. Charlie has other plans.