Depp, 46, is best known for his work on TV's "21 Jump Street," as well as in the quirky movies "Edward Scissorhands," "Ed Wood" and "Fear and Loathing in Las Vegas," and the "Pirates of the Caribbean" blockbuster franchise.
The father of two was previously declared People's Sexiest Man Alive in 2003.
Last year's winner was Australian actor Hugh Jackman.
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