One day Mendes caught the eye of an agent who convinced her to pursue acting more steadily. She worked her way up through commercials to music videos, including an appearance in Will Smith's video "Miami" and the Pet Shop Boys music video for "Se a vida é (That’s the way life is)" in 1996 and Aerosmith's video "Hole in My Soul" in 1997, to guest roles in soap operas and supporting film roles. Her first film appearance was in the direct-to-video Children of the Corn V: Fields of Terror.
Mendes received her first big-screen break when she appeared in Training Day. That performance led to roles in Stuck on You, Once Upon a Time in Mexico, and as the female lead in the comedy Hitch opposite Will Smith. Her role in Once Upon a Time in Mexico also earned her a nomination at the Teen Choice Awards.
Mendes has also been in commercials for Fruit Gushers(where her head morphed into an enormous orange), Revlon, and the famous Levi's "Superlow" commercial with the singing bellybuttons. Mendes costarred in Ghost Rider with Nicolas Cage, and recently starred alongside Joaquin Phoenix, Mark Wahlberg, and Robert Duvall in the film We Own the Night, and Gabriel Macht, Samuel L. Jackson and Scarlett Johansson in The Spirit.
Along with acting, Mendes is employed by Revlon Cosmetics as an international spokeswoman. She joins such actresses and models as Julianne Moore, Halle Berry and Cindy Crawford, who appear in Revlon's television and print ads. She is also a supporter and active participant in Revlon's campaign to raise funds for breast cancer research.
Mendes appeared naked in Flaunt Magazine. Mendes said about the shoot, "I actually did a little nude shot. You won't see anything. I was covering myself... but I love 'Flaunt.' I think their artwork is some of the best artwork out there as far as photography is concerned, so I took it off. I felt really comfortable, it was fun. There's something really liberating about it." She also appeared nude in an ad for Calvin Klein's Secret Obsession perfume. In this ad she is seen rolling nude in a bed, exposing her right breast and nipple.
In December 2007, People for the Ethical Treatment of Animals (PETA) used a nude photo of Mendes for their anti-fur campaign alongside the tagline "Fur? I'd rather go naked." Mendes is also a spokesmodel for the 2008 Calendar of Campari, inspired in fairy tales, by photographer Marino Parisotto.
In 2008, Mendes starred in The Women, a comedy ensemble film featuring Meg Ryan, Annette Bening, Jada Pinkett Smith, and Debra Messing. The film, which was produced by Victoria Pearman and Mick Jagger of Jagged Productions, Bill Johnson of Inferno Productions, and English, is being released by Picturehouse, a joint venture of HBO and New Line Cinema.