The 'Knocked Up' actor will become only the ninth male cover star in the magazine's history when he appears in the March 2009 issue. It is believed he will pose alongside model Hope Dworaczyk.
Other men to have graced the cover of the adult publication include Peter Sellers, Steve Martin, Jerry Seinfeld and Burt Reynolds.
Meanwhile Playboy's risque reputation was tarnished this week when a former Playmate of the Year, Sara Jean Underwood, claimed the magazine's founder Hugh Hefner - who is renowned for having several live-in lovers - imposes strict rules on his girlfriends.
Sara said: "They're young girls and they should be out there partying, but they had strict curfews and had to be in by nine o'clock."
Three of Hugh's girlfriends, Kendra Wilkinson, Bridget Marquardt and Holly Madison - stars of reality TV show 'Girls Next Door' - left him last year.
Hugh, 82, is now dating 19-year-old twins Karissa and Kristina Shannon and Crystal Harris, 22.
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