The 'Green Lantern' and 'Transformers 2' stars will front the autumn print and in-store activity for the brand's premium Autograph range.
Supermodel David Gandy has also been unveiled as the face of its Collezione sub-brand.
Completing the new line-up for this season are models and actresses Sophie Byron, Suki Waterhouse and Louise De Chevigny. They will feature in an in-store and online print campaign for Limited Collection, shot by fashion photographer Rankin, who also photographed its kidswear campaign.
M&S executive director of marketing Steve Sharp said the print campaign starring Reynolds and Huntington-Whitely totally "encapsulates the Autograph brand" as they were "beautiful, exclusive and absolutely contemporary".
"It’s a very different campaign for M&S as it’s the first time we have focused on one of our brands in this way. We are very proud of the result."
Reynolds said that he grew up with the M&S brand in Canada. "Going into an M&S store with my family or friends always gives me a beautiful pang of nostalgia. The Autograph collection is a modern take on the classic style I love and feel most comfortable wearing. The pieces in this collection are lasting staples that'll never go out of style."
Model Gandy described the tie-up as a "dream come true".
Twiggy, Lisa Snowdon and Jamie Redknapp will continue to appear in print ads and in-store, but they will be only be modelling the core M&S Woman and M&S Man ranges.