The multi-million pound campaign, created by Mother, will feature the singer, best known for her international number one hit 'Mercy', acting in one of a series of 30 and 60-second TV spots soon to launch across Europe.
Coca-Cola chose Duffy to make the ads attractive to younger female viewers aged 20-35. She follows in the footsteps of actress Kim Basinger who previously starred in ads for the brand.
Duffy will appear in the campaign alongside other "strong, sassy young women" celebrating their right to stand up to the pressures of modern day life.
Duffy said: "I love the attitude of this new Diet Coke ad. I drink so much of the stuff, they were either going to give me shares in the company or put me in the advert."
Cathryn Sleight, Coca-Cola Great Britain marketing director, said: "Our campaigns are well known for tapping into a powerful social and cultural zeitgeist and Duffy is a great embodiment of today's modern female attitudes.
"She has a strong appeal with our core female audience and we're confident that this campaign will become just as iconic as previous Diet Coke advertising campaigns."