The 36-year-old Hangover star scooped the honour over competition including The Hunger Games actor Liam Hemsworth and Captain America star Chris Evans.
Cooper told the magazine: "I think it's really cool that a guy who doesn't look like a model can have this [title].
"I think I'm a decent-looking guy. Sometimes I can look great, and other times I look horrifying."
Other stars featured in this year's 'Sexiest Man Alive' list include Twilight's Robert Pattinson, Justin Timberlake, Justin Theroux, Luther star Idris Elba, Tim McGraw, Joel McHale and Ryan Gosling.
Ryan Reynolds was named 'Sexiest Man Alive' for 2010, while previous winners have included Brad Pitt, Johnny Depp and George Clooney.
People's 'Sexiest Man Alive' issue hits newsstands on Friday.
Look at People's top 12 Sexiest Men Alive here.