Having run across an ad for an open casting call and attending her first audition, Rodriguez beat 350 other applicants to win her first role in the low-budget 2000 independent film, Girlfight. Rodriguez's performance as Diana Guzman, a troubled teen who decides to channel her aggression by training to become a boxer, was recognized by both critics and audiences, but despite major industry buzz of a possible Academy Award nomination, she did not receive the Oscar nod. Rodriguez did however accumulate several other significant awards and nominations for the role in independent circles, including major acting accolades from the National Board of Review, Deauville Film Festival, Independent Spirit Awards, Gotham Awards, Las Vegas Film Critics Sierra Awards, and many others. The film itself took home top prizes at both the Sundance and Cannes Film Festivals.

Subsequently, she has had notable roles in other successful movies, including The Fast and the Furious, Resident Evil, Blue C