The 28-year-old star of "Don Jon," "The Avengers" and "Lost in Translation" previously held the title in 2006. She is the only person to be so honored by the magazine twice.
Johansson, who is featured on the cover and in a photo layout for Esquire's November issue, told the magazine she is ready for a break after working non-stop for more than a year.
"I'm exhausted and this is my last day in the world," she said. "This is the last day, and this is the last piece of work. Then I'm taking a month-long vacation. But I'm not going anywhere, which just makes it more of a staycation. There's luxury in being near home. When you spend a lot of time, like I do, just standing around and waiting, or being moved from place to place, every minute gets consumed by something someone else has set up for you."