South African-born Theron, who also starred in the remake of 'The Italian Job', will be the new face of J'adore, the designer's fragrance that launched in 2000.
Ads will start appearing in the US next month, and Dior's artistic director John Galliano and photographer Nick Knight are understood to have overseen all aspects of the advertising campaign.
Pamela Baxter, president and CEO of LVMH Perfumes & Cosmetics, said: "Ms Theron was chosen because she represents modern femininity and embodies the spirit and energy of Dior. She is a classic beauty."
Theron will see herself pitted against fellow actress Nicole Kidman, who is starring in an ad campaign for Chanel No 5, which breaks around the same time. The Chanel campaign is directed by Baz Luhrmann, who helmed 'Moulin Rouge', which also starred Kidman.
Theron is the latest Hollywood actress to sign up to a fashion and beauty brand. Hilary Swank features in underwear ads for Calvin Klein, as does Scarlett Johansson, while Diane Kruger and Chloe Sevigny will star in Louis Vuitton's autumn campaign.
Theron won an Oscar this year for her portrayal of serial killer Aileen Wuornos in 'Monster', a role that required her to put on weight and wear heavy make-up. Theron has also starred in 'The Cider House Rules' and appears this year in 'The Life and Death of Peter Sellers' as Britt Ekland.
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