By taking the title, the 40-year-old Madrid-born actress now joins a group that includes Angelina Jolie, Charlize Theron and Scarlett Johansson.
But Cruz — described as "impossibly beautiful" by Esquire — is unlikely to be carried away by the honour.
An Oscar winner for her role in Woody Allen's Vicky Cristina Barcelona, Cruz has never achieved massive success in Hollywood but remains deadly serious about her acting.
In her interview with Esquire, she describes lying about her age to be able to watch films by her friend mentor, Spanish cinema great Pedro Almodóvar. Cruz has star in five of her films and is about to appear in another, although she is coy about the details.
She is also serious about her marriage to fellow actor Javier Bardem who she first met in 1992 when they starred together in the classic Spanish comedy Jamon, Jamon.
The couple have two children together, but that part of Cruz's life remains strictly off bounds to the press.
Cruz however, has not always been shy about her political beliefs. Recently she was named "idiot of the week" by the conservative US broadcaster Fox News for speaking out against Israel's bombing of the Gaza Strip.
Together with Spanish director Pedro Almodovar and other big names in Spanish showbiz, Bardem and Cruz called for the EU to halt Israel’s military attack in Gaza.
Cruz later wrote a clarifying letter in USA Today newspaper in the face of the barrage of criticism she was receiving, with many opponents calling her an "anti-Semite".
"I don't want to be misunderstood on this important subject," Cruz wrote.
"I'm not an expert on the situation and I'm aware of the complexity of it. My only wish and intention in signing that group letter is the hope that there will be peace in both Israel and Gaza."