In its November issue, which hits newsstands on October 16, Theron, 32, talks about her new movie, politics, being from South Africa and her feelings about the United States, where she recently earned dual citizenship.
The long-legged, blonde beauty also shows a penchant for drinking, cussing and smoking, and she tears up when talking about the recent death of her dog.
The issue annually is one of Esquire's most widely read, and it generates debate among readers, D'Agostino said.
He added that every year the Sexiest Woman exudes some sense of individuality, and that there is no set of criteria or rules by which the magazine's editors, writers and other contributors pick the titleholder.
D'Agostino did say the magazine likes to choose someone based on how current they are in pop culture. After taking time off following 2005 film "North Country," Theron is back with two movies, "Elah" and "Battle in Seattle," this year and has several others set for release next year and beyond.
Theron follows a long line of actresses and others claiming the Sexiest Woman title at the 74 year-old magazine. Last year's titleholder was Scarlett Johansson and the year before her, Jessica Biel.