The sequel to Scary Movie begins with a parody of The Exorcist, in which Megan Voorhees (Natasha Lyonne), is possessed and two priests, Father McFeely (James Woods) and Father Harris (Andy Richter), must drive the demon out. The exorcism doesn't go as planned, and a chain of The Exorcist-like vomiting occurs. Megan insults McFeely's mother and he shoots her in the head.
One year later, Cindy Campbell (Anna Faris), Brenda Meeks (Regina Hall), Ray Wilkins (Shawn Wayans) and Shorty Meeks (Marlon Wayans) are at college, trying to live new lives, after the events in the previous movie. (Although all of them died in Scary Movie, in a deleted scene, Brenda says her death was a near death experience, and Cindy was never officially declared dead.) Cindy and Brenda get tagged by a dorky girl, Alex Monday (Tori Spelling); Ray, who is still confused by his sexuality, has two new friends, Tommy (James DeBello) and Buddy (Christopher Masterson); while Shorty is still the same stoner he was in the last movie.
The story begins when a college teacher, Professor Oldman (Tim Curry) and his wheelchair-bound assistant Dwight (David Cross) plan to study the paranormal activity at Hell House, with the clueless teens as bait and for Oldman to get action with the college girls. Newcomer Theo (Kathleen Robertson) also becomes part of the study group.
When Cindy arrives at the Hell House, she meets a talking Amazon parrot who is vulgar and slanderous, and the caretaker, Hanson (Chris Elliott), who has great people skills and a genetically malformed little hand. After some weird incidents on that night (Cindy being beaten up by a cat, a toy clown attacking Ray after he had sex with Brenda, Shorty getting attacked and smoked by a weed-monster, and Alex having sex with a ghost and it "humps" her. The teens finally learn about the professor's plan and try to escape the mansion.
The professor gets killed by a female ghost with disfigured features as the ghost of Hell House's owner, Hugo Kane, seals all exits of the manor to prevent the surviving occupants from escaping. Realizing that killing the ghost is the only way out, the teens are equipped with several technological devices by Dwight that serve to harass and injure the spectral enemy. They are pursued all throughout the mansion. Cindy is chased by an undead skeleton and Brenda rips his bones. Shorty meets the ghost who killed the professor but puts a paper bag on her face and has sex with her. Hanson gets possessed, and Cindy, Brenda and Theo parody Charlie's Angels to get him, but end up beaten up. Eventually, they use Cindy as bait to lure the Kane ghost to a device that ultimately destroys him.
Two months later, taking care of the parrot though he despises her for talking too much, Cindy and Buddy are in a relationship and go out on a walk until ......................