Fred Flintstone (MARK ADDY) and his best pal, Barney Rubble (STEPHEN BALDWIN) are two blue-collar, prehistoric workers who've just landed jobs at the Bedrock rock quarry. While Barney is happy with their achievement, Fred isn't because he feels he should be enjoying his good news with an equally good woman by his side.
Across town, Wilma Slaghoople (KRISTEN JOHNSTON) is also unhappy, but for quite different reasons. The beautiful daughter of the Colonel (HARVEY KORMAN) and Pearl Slaghoople (JOAN COLLINS), Wilma can't see herself becoming her mother and living a pretentious and wealthy life. Nor is she interested in marrying Chip Rockefeller (THOMAS GIBSON), a handsome and debonair bachelor who owns much of Rock Vegas, the famous gambling city.
As such, Wilma hits the road and is taken in by Betty O'Shale (JANE KRAKOWSKI), a waitress at the local Bronto King, who believes Wilma to be a poor, "caveless" girl. The two become fast friends and eventually end up going on a double date with Fred and Barney. Soon, the two couples are inseparable, although a disaster at a Slaghoople dinner involving Fred's pet dinosaur, Dino, strains family ties.
Even so, Chip invites the foursome to his casino in Rock Vegas where they, along with The Great Gazoo (ALAN CUMMING), an alien sent to Earth to observe the "mating rituals" of stone age people, arrive and immediately begin having a good time, oblivious to the fact that Chip and his assistant, Roxie (ALEX MENESES), have ulterior motives.
As Chip sets his plan into motion, Fred and Barney must do what they can to get Wilma and Betty back into their lives and good graces, something that becomes rather difficult due to various obstacles thrown their way, including the presence of legendary rock and roll star, Mick Jagged (ALAN CUMMING).