Mendoza beat 27 other candidates to win Miss Venezuela 2007 on September 13, 2007, and became only the second woman representing the Amazonas state to win, following Carolina Izsak in 1991. She was crowned Miss Universe 2008 at the pageant in the Crown Convention Center, Nha Trang, Vietnam, on July 13, 2008. Mendoza became the first winner of the pageant from Venezuela since Miss Universe 1996's winner Alicia Machado, thus making her the first Venezuelan Miss Universe in the 21st century.
Miss Universe 2007 Riyo Mori crowned her with a tiara worth $120,000 USD. Her prize package includes cash, a year contract promoting Miss Universe, world travel, a rent-free, prestigious New York City apartment, luxury apartment and a gift bag stuffed with designer shoes, dresses and beauty products, a $100,000 stipend for a two-year course at the New York Film Academy and free access to famous fashion houses and beauty parlors. Mendoza will spend her year-long reign traveling the world to lecture on humanitarian issues and to promote education regarding HIV/AIDS.
As of June 2009, Mendoza as Miss Universe has traveled to Indonesia, Singapore, Italy, Vatican City, Spain, France, Nicaragua, Ukraine, Czech Republic, Bahamas, Russia, El Salvador, United Arab Emirates, Brazil, Dominican Republic, Puerto Rico, Bolivia, Argentina, Romania and Vietnam, in addition to numerous trips around the United States and her homecoming in Venezuela. Together with Miss Universe 1969 Gloria Diaz, Mendoza was also used as the goodwill ambassador of Venezuela-based technology firm Smartmatic to thank the Philippines for entrusting the company the success of their 2010 presidential elections.
Mendoza was a contestant on the 2012 season of the NBC reality competition series The Celebrity Apprentice. In Episode 3, "How Much is That Celebrity in the Window?", she was the winning project manager of her team on a task to create two themed living window displays for Ivanka Trump's clothing and accessory line, winning $20,000 for her charity, the Latino Commission on AIDS. Mendoza notes in Episode 11, "Winning by a Nose" that she holds the record for being brought back to the final boardroom, having done so six times by that episode. She came in sixth place after being eliminated in the 12th episode, "Jingle All the Way Home" (her seventh time in the boardroom), in which she was project manager of the losing team on a task to create a jingle and presentation for Good Sam Club.
On June 3, 2012, Mendoza served as one of the panel of judges for the Miss USA 2012 competition.
Mendoza was once kidnapped in Venezuela, and stated that the trauma taught her to remain poised under pressure. In 2001, she signed with Elite Model Management and was a finalist at the Elite Model Look International 2001, in Nice, France. She has worked with the companies Max Mara and Costume National, where she modeled in New York City, Italy, Germany, France, Greece and Spain for Versace, Roberto Cavalli and other fashion designers. She speaks Spanish, English and Italian. After Elite, she signed to Trump Model Management, and in Milan, Names Model Agency.
After photos of Mendoza modeling naked for a jewelry firm surfaced, officials from the Miss Universe Organization decided against penalizing her, saying that the candid photos were not pornographic but "artistic in nature, and they don't have an ounce of pornographic content to them."
On March 27, 2009, Mendoza documented a visit to Guantanamo Bay detention camp on her Internet blog. In it, she was quoted as saying, "[Guantanamo] was such a relaxing place, so calm and beautiful". She also stated that when she visited the detainees camps, "...we saw the jails, where they shower, how they recreate themselves with movies, classes of art, books. It was very interesting". In her home country, Venezuela, the issue became the talk of the town, with the president, Hugo Chávez, reconsidering the praise he had previously given her. The Miss Universe Organization has replied that "...[her] comments on her blog were in reference to the hospitality she received while meeting the members of the U.S. military and their families who are stationed in Guantánamo". On 1 April 2009, the entry vanished from her blog.