Plot
In Prague, Blade searches for his mentor Abraham Whistler, who was thought dead after being attacked by Deacon Frost but was instead turned into a vampire and held prisoner by them for two years. After interrogating vampire Rush on Whistler's whereabouts, Blade rescues Whistler and cures him of his vampirism. Whistler meets Scud, Blade's young, gifted new technician.
A pandemic is turning vampires into "Reapers", primal, mutant creatures with a ravenous thirst for blood and a highly infectious bite that transforms both humans and vampires alike. The original carrier of the Reaper strain and cause of the pandemic is Jared Nomak, who bears hatred toward the vampire race. To combat the Reapers, vampire overlord Eli Damaskinos sends his trusted servant Asad and his daughter, Nyssa, to strike a truce with Blade. Knowing humans will be the Reapers’ next target after vampires, Blade reluctantly allies himself with them. He teams up with the Bloodpack, an elite group of vampires originally assembled to kill him, consisting of Asad, Nyssa, Reinhardt, Chupa, Snowman, Priest, Verlaine, and her lover, Lighthammer. As Reinhardt openly challenges him to fight, Blade, in response, attaches an explosive to the back of his skull to keep him in line. They investigate a vampire nightclub where they encounter the Reapers and discover they are immune to most vampire weaknesses except for UV exposure. Nomak arrives and tries to recruit Blade to his cause, but the latter refuses. Blade fights Nomak but cannot kill him due to his immunity to his weapons before the sun rises, and Nomak retreats. Lighthammer is bitten but conceals the bite from the group, while Priest is bitten and in the process of turning before being mercy-killed through exposure to sunlight.
Whistler returns to the group after locating the Reaper nest beneath the sewers. Nyssa dissects a dead Reaper and learns that their hearts are encased in durable bone. Scud and Whistler issue new UV weapons for the team and a UV-emitting bomb to take out the entire nest. Entering the Reaper nest at dawn, Lighthammer transforms into a Reaper and kills Snowman. Verlaine sacrifices herself to kill Lighthammer by exposing them both to sunlight. Chupa turns on Whistler in retaliation for Priest's death, but Whistler secretly releases a cartridge of Reaper pheromones into the air, luring a horde that kills and devours Chupa. Asad and Nyssa are ambushed, and Asad is killed. Blade saves Nyssa and detonates the UV bomb, killing all the Reapers except Nomak. Nyssa and Reinhardt manage to evade the blast, but Nyssa is seriously injured until Blade allows her to drink his blood to survive.
Damaskinos's forces arrive and capture Blade, Whistler, and Scud. Damaskinos reveals that the Reapers exist due to his efforts to engineer a stronger breed of vampires devoid of their natural weaknesses. Nomak, the first Reaper, is his own son, whom Damaskinos considers a failure. Scud reveals himself to be one of Damaskinos's familiars, but Blade, who already suspected this, kills him with the explosive he planted on Reinhardt earlier, which Scud originally thought was a dud until Blade secretly swapped it with a real explosive. He plans to harvest Blade's blood to develop an immunity to sunlight and create a new, invincible breed of vampires. Whistler frees himself, escapes from Reinhardt, and rescues a weakened Blade. Reinhardt shoots at the two, but Blade falls into Damaskinos's blood pool, restoring his strength. He fights his way through Damaskinos's henchmen and kills Reinhardt.
Nomak enters Damaskinos's stronghold, seeking revenge on his father. Nyssa, seeing how her father holds no regard for his own offspring, betrays Damaskinos by sealing off their escape route, and Nomak kills Damaskinos after failing to negotiate with him. Nomak then bites Nyssa, infecting her with the Reaper virus. Blade and Nomak engage in battle, and he manages to stab Nomak through his encased heart. Wanting to end his suffering, Nomak kills himself with Blade's sword. Fulfilling Nyssa's dying wish, Blade takes her outside and embraces her as her body disintegrates from the sunrise. Sometime later in London, Blade tracks down Rush to a strip club booth and kills him.
