Jennifer Willis (Shanelle Workman) is to have an interview with Dr. Henry West M.D. (Richard Doyle), professor of necrobiology, at his house. Her boyfriend, Rick Taylor (Josh Keaton), comes along so nothing bad happens. Just as Rick is about to propose to Jennifer, the two are attacked by Dr. West's experiments, kidnapping Jennifer and leaving Rick mortally wounded. Rick knocks over a sarcophagus revealing a mask. Close to death, the Terror Mask (Jim Cummings) calls out to Rick, saying it will save him and help save Jenny if he puts it on. Having no choice, Rick puts the mask on and is transformed into a hulking beast powered by the blood of others.

Rick follows Dr. West and Jennifer through other dimensions and time periods and learns of Dr. West's plan to bring dark deities, known as "The Corrupted", into this world by sacrificing Jennifer. Dr. West believes The Corrupted will resurrect his dead love Leonora, who bears an uncanny resemblance to Jennifer and originally died of cholera. The Corrupted intended to lay waste to Earth instead. It is revealed that Dr. West and the Corrupted had previously resurrected Leonora, but she was brought back as a demonic savage. West tried to contain her and bring her back completely, but one instance she escaped; Dr. West later found her holding a porcelain doll, horrified at the fate of the child she took it from. West was later summoned away from the town of Arkham and his home on a pointless errand, only to discover that the town's populace found out about Leonora, and imprisoned her to be burned as a witch. Rick encounters Leonora while traveling through time, emerging near the alit wickerman cage as the townsfolk are turned into monsters by the Corrupted. In an attempt to save Leonora thinking she was Jennifer, Rick was attacked by her demonic form, forcing him to kill her. A young Dr. West witnesses Rick stomping on her and loses his morality, vowing to tear down the gates of heaven and ascending on a pile of corpses, built from the townsfolk of Arkham and topped with Rick's dead body.

In the end, Rick succeeds in rescuing Jennifer and thwarting West's plans; however, leader of the Corrupted, the Overlord emerges, summoned from the killings Rick committed through the game and constructed from the bodies of 10,000 monsters. The Mask informs Rick that he knew that Rick's killing would release it, stating that he wanted the Corrupted to know that it was the Mask that stopped them, and for that to happen, he needed to let them out. Rick and the Mask manage to kill it and sate the Mask's thirst for vengeance, but in the process, a stray spirit possesses Jennifer. Believing his deal with the Mask to be done, he tries to pry it off; however, aware of Jennifer's possession, it refuses. It is implied from West's reaction that the stray spirit is of Leonora's.