Mendes was born in Miami, Florida, to Cuban parents, and was raised in the Los Angeles suburb of Glendale by her mother after her parents' divorce; Mendes has said that her mother "suffered so much to make my life OK" during her early years. Mendes was raised a Roman Catholic and aspired to be a nun. She is also fluent in Spanish. As a child, Mendes was teased about her buck teeth.
Mendes never saw herself as an actress while she was young and pursued other interests. She attended Hoover High School in Glendale and later attended California State University, Northridge to studymarketing, but dropped out after wanting to begin an acting career. She studied acting under the acting teacher, Ivana Chubbuck.
Mendes caught the eye of an agent who convinced her to pursue acting more steadily. She appeared 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 costarred in Ghost Rider with Nicolas Cage, who she was to work with again in Bad Lieutenant: Port of Call New Orleans in 2009, and also 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. In March 2011, it was announced that Mendes will be a new spokeswoman for Thierry Mugler's Angel fragrance.
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.
On September 4, 2008, Mendes announced she was launching a line of bed linens available in Macy's stores. In October, she toured various stores in Europe including Harrods to promote Calvin Klein's Seductive Comfort line of lingerie.
In August 2010, Mendes appeared in a Funny or Die video spoof, selling her "S.EX. tape". She also sang for the Funny or Die music video "Pimps Don't Cry," a song featured in The Other Guys, released on August 6, 2010.
In early 2008, Mendes entered a rehabilitation facility in Utah for several weeks for substance abuse problems. In a statement, her representative said that she had been "working hard for the past year and made a positive decision to take some much-needed time off to proactively attend to some personal issues that, while not critical, she felt deserved some outside professional support."
In 2008, Mendes very pointedly broke from her co-stars of The Women by not offering support to any presidential campaign, noting that she considered her ballot preference private. After the election, she expressed disappointment at not receiving an invitation to Barack Obama's inauguration party.
Mendes and her boyfriend, filmmaker George Augusto, have been together since 2002. "I don't wanna have kids ... I love the little suckers; they're so cute. But I love sleep so much, and I worry about everything," she told Marie Claire. "I feel like the institution of marriage is a very archaic kinda thing. I don't think it fits in my world today."