After a dying Voodoo queen, Mama Loa, chooses an adopted apprentice, Lisa Fortier as her successor, her arrogant son and true heir, Willis, is outraged.
Seeking revenge, he buys the bones of Mamuwalde the vampire from the former shaman of the voodoo cult and uses voodoo to resurrect the vampire to do his bidding. However, while it brings Mamuwalde back to life, he bites Willis upon awakening. Willis now finds himself in a curse of his own doing: made into a vampire hungering for blood and a slave to the very creature he sought to control.
Meanwhile, Justin Carter, an ex-police officer with a large collection of acquired African antiquities and an interest in the occult, begins to investigate the murders caused by Mamuwalde and his growing vampire horde. Justin meets Mamuwalde at a party Justin hosts to display the African collection pieces before being moved to the University's museum. They discuss the artifacts, unbeknown to anyone else, that were from the region of Africa Mamuwalde hails from, including pieces of jewelry once worn by his late wife Luva.
Mamuwalde also meets Justin's girlfriend, Lisa Fortier, at the party and he discovers that Lisa is naturally adept at voodoo. Lisa discovers Mamuwalde's true nature after a friend of hers, Gloria, falls victim to his bite and is resurrected as a vampire who nearly feeds on her, if not for Mamuwalde's intervention. He later asks her for help to cure him of his vampire curse.
Justin, with the help of L.A.P.D. Lieutenant Harley Dunlop, pulls together several other cops to go to the Mamuwalde residence to investigate the recent deaths. While Lisa is performing the ritual to cure Mamuwalde, using a voodoo doll fashioned to look like him, Justin, Harley and their men raid the house, fighting against Blacula's vampire minions which include several friends of theirs. Willis is killed during this scuffle. Justin manages to find Lisa and Mamuwalde and interrupts the ritual. Lisa refuses to help Mamuwalde after she witnesses him kill the other police officers in the house in a fit of rage.
After realizing that Lisa is no longer willing to help Mamuwalde, he rejects his human nature and decides to convert Justin into a vampire. Shouting he is only "Blacula", Lisa stabs the prince's voodoo doll with Justin's arrows repeatedly. Blacula screams out in pain from Lisa's voodoo doll attacks, the movie ending suddenly on this and leaving his fate ambiguous.
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