In 1780, African prince Mamuwalde goes to Transylvania to seek the help of Count Dracula in suppressing the slave trade. Dracula refuses, however, and insults Mamuwalde by making a pass at his wife, Luva. After a scuffle with Dracula's minions, Mamuwalde is bitten by Dracula and transformed into a vampire while dead. Dracula then curses him with the name "Blacula" and imprisons him in a sealed coffin in a crypt hidden beneath his castle while leaving Luva with Mamuwalde to die in the chamber.
In 1972, two interior decorators, Bobby McCoy and Billy Schaffer, find the coffin and are informed that the coffin was previously owned by Count Dracula, who was killed by Van Helsing in the late 1800s (much like in the original Dracula novel). After purchasing the coffin and shipping it to Los Angeles, Bobby and Billy open the coffin, only to become Mamuwalde's first victims. At the funeral home where McCoy's body is laid, Mamuwalde spies on mourning friends Tina Williams, her sister Michelle, and Michelle's boyfriend, Dr. Gordon Thomas, a pathologist for the Los Angeles Police Department. Mamuwalde becomes infatuated with Tina, believing her to be the reincarnation of Luva due to her identically resembling the latter. Thomas notices oddities with McCoy's death that he later concludes to be consistent with vampire folklore. Mamuwalde follows Tina after leaving the funeral home but unintentionally frightens her. Tina runs away from him, and Mamuwalde loses her when he is hit by a cab. He then kills the cabbie, Juanita Jones, turning her into a vampire.
Thomas, Michelle, and Tina celebrate Michelle's birthday at a nightclub, and Mamuwalde shows up to return Tina's purse, which she'd dropped the night before. Thomas answers a phone call from the funeral director, who informs him that McCoy's body has gone missing. Mamuwalde asks Tina to see him again the following evening, but they are interrupted by Nancy, a photographer who takes a photograph of them together. Soon after, Mamuwalde kills Nancy and destroys the photo she just developed, which shows Mamuwalde conspicuously absent.
Soon after, a police car pulls up near Nancy's house. As the officer is getting out, he sees Nancy stumble onto the porch. He goes over to check on her as she's asking for help. When he picks her up to go get help, Nancy bites him, turning him into a vampire.
The next evening, Mamuwalde visits Tina at her apartment and shares how Dracula enslaved him and Luva and how he was cursed with vampirism. He and Tina then spend the night together.
Thomas, Lt. Jack Peters, and Michelle are meanwhile following the trail of murder victims, as Thomas begins to suspect a vampire of being the perpetrator. After Thomas and Michelle dig up Schaffer's coffin, the corpse rises as a vampire and attacks Thomas, who fends him off and drives a stake through his heart. Michelle now realizes the truth and that McCoy could still be out there. Telling Peters won't work, because they need to show him what's going on, and to do this, they'd need to thaw out the corpse of Juanita Jones. Thomas calls the morgue and instructs Sam, the attendant, to take Jones' body out of deep freeze and leave the room and lock the door. Sam rolls her body out, but neglects to lock the door due to a distracting phone call. Suddenly the door opens, and an undead Jones rises and immediately attacks and kills him. Moments later Thomas and Peters arrive at the morgue to find blood smeared on the corridor wall near the payphone where Sam answered the call, but no sign of Sam himself. They walk into the exam room by the freezer, where Peters sees a sheet-covered body lying on a gurney and pulls the sheet back to reveal Jones rising to attack him. Thomas keeps her at bay with a Christian cross long enough to open the window blinds and expose her to sunlight, destroying her.
That evening, Thomas, Michelle, and Tina are enjoying drinks at the club when Mamuwalde arrives to pick Tina up. Thomas questions Mamuwalde about vampires and makes it known that the police are planning a search for the vampire's coffin, provoking an uncomfortable Mamuwalde and Tina to leave. Soon after, remembering that Nancy never gave Michelle her birthday photos, Thomas searches Nancy's house and finds a photo of Tina standing in front of an invisible Mamuwalde. He correctly deduces that Mamuwalde is the vampire they seek, and that Mamuwalde and Tina are together. Thomas rushes to Tina's apartment, finding them embracing. Thomas and Mamuwalde briefly struggle, but Mamuwalde knocks Thomas unconscious and flees, killing a police officer in a nearby alley as he escapes. After McCoy is seen walking the streets of Los Angeles, Thomas, Peters, and several police officers track Mamuwalde to his warehouse hideout. They locate a nest of several vampires there, including McCoy, and destroy them, but Mamuwalde escapes.
Mamuwalde hypnotizes Tina into going to his new hideout at a nearby underground chemical plant while Thomas and the police pursue him. Mamuwalde dispatches several of the officers, but one of them accidentally shoots and mortally wounds Tina. To save her life, Mamuwalde transforms her into a vampire. Mamuwalde fights the police, one of whom locates the coffin and alerts Thomas and Peters. However, Peters kills a newly turned vampiric Tina with a stake, having believed Mamuwalde would be in the coffin instead. Devastated and feeling he has no purpose to live after losing Luva again, Mamuwalde commits suicide by climbing the stairs to the roof where the morning sun destroys him. Thomas and Peters witness Mamuwalde's flesh melting away with maggots coming out of his face until only his skeleton remains.
After a series of confrontations and tragic losses, Mamuwalde (Blacula) is ultimately defeated and the threat he poses to Los Angeles comes to an end.
The film’s climax resolves the central conflict by ending Mamuwalde’s reign as Blacula, bringing closure to his centuries-old curse and his doomed quest for lost love. The ending underscores the tragic nature of his character: a man transformed by cruelty, whose longing for connection is ultimately his undoing. In classic vampire fashion, the conclusion restores order, but not without a sense of melancholy for the prince who was both victim and monster.
