In 1967, a pregnant woman is attacked by a vampire while giving birth. Doctors are able to save her baby, but the woman dies of infection.
Thirty-one years later, the child has become the vampire hunter Blade. He raids a rave club owned by the vampire Deacon Frost. Police take one of the vampires to the hospital, where he feeds on hematologist Karen Jenson and escapes. Blade takes Karen to a safe house where she is treated by his old friend Abraham Whistler. Whistler explains that he and Blade have been waging a secret war against vampires using weapons based on their elemental weaknesses, such as sunlight and silver. As Karen is now "marked" by the bite of a vampire, both he and Blade tell her to leave the city.