Blade (WESLEY SNIPES) is a half-human, half-vampire whose mission in life has been to find and kill all vampires. His mentor, Whistler (KRIS KRISTOFFERSON), the man who invented a serum to allow Blade to be in the daylight - thus his nickname of "Daywalker" - has been missing for years and presumed dead.
Yet, Blade eventually finds, rescues and gives him an antidote to counter the vampirism that now afflicts him. Blade's new technician/inventor partner, Scud (NORMAN REEDUS), isn't thrilled to have the old man back in their fold, but the three soon learn they have bigger fish to fry. It seems that a mutant super-vampire, Nomak (LUKE GOSS), is on the loose and killing other vampires.
Accordingly, vampire overlord Damaskinos (THOMAS KRETSCHMANN) has sent his daughter, Nyssa (LEONOR VARELA) and her co-warrior, Asad (DANNY JOHN JULES), to convince Blade and his team to join the vampires in an unusual alliance to find and kill Nomak before he infects and creates a multitude of other super-vampires, known as Reapers.
Realizing the potential global Armageddon Nomak and the others could wreak on the world, Blade cautiously agrees and then meets the Bloodpack, a group of vampires led by Reinhardt (RON PERLMAN) that were specifically trained to find and kill Blade. Among its members are Chupa (MATT SCHULZE),
Priest (TONY CURRAN), Snowman (DONNIE YEN), Lighthammer (DAZ CRAWFORD) and
Verlaine (MARIT VELLE KILE), and they're just as unhappy about working with Daywalker as he is to allow them to live.
Nevertheless, the unlikely team then sets out to find Nomak only to discover, among other things, that he and the other reapers are more powerful than originally thought.