The lead character from the previous two movies, Cindy Campbell (Anna Faris), is now a television newswoman and begins investigating the deaths surrounding a mysterious videotape and its connection to crop circles appearing on the farm of Tom Logan (Charlie Sheen). The connection eventually leads Campbell to work with the President of the United States (Leslie Nielsen) to stop an alien invasion of Earth.

- Cindy (Anna FarisScary Movie 3 is a newswoman, working for The Morning News. Now looking after her deceased sister's orphaned child (Cody), she is determined to find out the connection between 'crop circles', aliens and a video tape. The main thing that clashes with her voyage is her job, which will not allow the news to get out due to the fact that, according to her boss, the news is all to do with sex, violence and the weather. - Tom (Charlie SheenScary Movie 3 is an ex-minister, a widower who lost his wife in a horrific car accident which is explained later on the film. He, like Mel Gibson's character in the horror film Signs, wakes up to find mysterious patterns in his field (except in this movie it's a rectangle formed by knocked down crops, with some parts of the field left up to reveal the huge words 'ATTACK HERE' and an arrow pointing to exactly where Tom, George and Tom's daughter are standing to examine the work). A seemingly caring and wise man, he loves his family, although doesn't seem to approve of his brother's intended occupation (a rapper). - George (Simon RexScary Movie 3 is Tom's younger brother and aspiring rapper. Friends with rap club owner Mahalik (Anthony Anderson), he is clumsy, somewhat lacks common sense, and is known for unintendedly causing trouble and subsequently getting thrown out of places (he accidentally wore a Klan-like hood in the middle of a rap battle and ruined a funeral when he thought that the cadaver was still alive). George also seems to have some feelings for Cindy and their relationship is a recurring theme in the film. Cody looks up to him as a father figure. - Cody is an orphan who seems to have visions of the mysterious force that is the heart of the killer videocassette. Cody has an amazing ability to be able to end up in a difficult situation and get out of it (in the film, he's hit by a car (twice), is blown out of a window, is hit on the head with a shovel and basketball, and with a baseball bat). He is another one of the people who watches the video tape.He also has the ability to see into the future.Leslie Nielsen's character of The President, repeats his last line from Airplane!, "Just wanted to wish you both good luck...we're counting on you.". That film was co-directed by David Zucker.