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The 37-year-old follows in the footsteps of model Cara Delevingne and Prince Harry’s ex-girlfriend Cressida Bonas, who have also won the honour.
Awarding the title to an American is considered a break with tradition for the quintessentially British glossy journal.
Writer Rebecca Thorpe said the choice is a departure from the “toffs, mischief-makers and social media mavens” who have made it on to earlier lists.
She added: “Meghan Markle is none of the above, although she is worthy of the accolade.”
The former Suits actress married Harry in a fairy tale wedding at Windsor Castle in May.
Meghan will feature in the October edition of the magazine, which said she is popular with readers because of the “unmissable quality that makes her the one for whom heads turn”.
Just this week she wowed onlookers when she wore a stunning tuxedostyle dress to a charity performance of hip hop musical Hamilton, at London’s Victoria Palace Theatre.
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