McFarlane will proceed as the executive producer on a re-imagination of the cartoon that follows the life of two cavemen families, the Rubbles and the Flintstones, and is set in the unreal prehistoric city of Bedrock.
Making allusions to The Simpsons and his individual hit adult animation series Family Guy, MacFarlane asserted: "I think America is finally ready for an animated sitcom about a fat stupid guy with a wife who's too good for him."
Seth has been a lasting fan of The Flintstones that was formerly made by Hanna-Barbera and broadcasted between 1960 and 1966 - and claimed the first cartoon picture he ever drew when aged two was of leading character Fred Flintstone.
He has as well assured not to modify the format too far, though he is definite to add his individual trademark name of humour.
MacFarlane insisted the character will looks the similar as in the original series however he'll establish latest technology, as "what is the animal version of an iPad?"
The program will appear on the Fox network in the United States - which airs Seth's series' Family Guy, The Cleveland Show and American Dad! - it is due to go through production in the year, with broadcast date fixed for 2013.
President of Entertainment at Fox, Kevin Reilly, added: “The Flintstones are among the funniest and most beloved characters in television history, and we can't wait to introduce them to a whole new generation.”
"Fox has long been home to iconic families like the Simpsons and [Family Guy's] the Griffins, so I have no doubt that the Flintstones and the Rubbles are going to fit right in on our air."