[3] Outside of film, Rodriguez played Ana Lucia Cortez in the drama television series Lost (2005–2006; 2009–2010), and voiced Liz Ricarro in the English-language translation of the anime Immortal Grand Prix (2005–2006).

She reprised her roles in video game spin-offs of Avatar and Fast & Furious, and also appeared in True Crime: Streets of LA (2003), Driver 3 (2004), Halo 2 (2004), and Call of Duty: Black Ops II (2012).

[10] She briefly attended business school before quitting to pursue a career in acting, with the ultimate goal of becoming a screenwriter and director.

She was partly raised by her devoutly religious maternal grandmother, and was brought up as a Jehovah's Witness (her mother's religion), although she has since abandoned the faith.

[12][13] A DNA test of Rodriguez, performed by the television program Finding Your Roots, found that her ancestry is 72.4% European, 21.3% African, and 6.3% Native American.

She stated on the show that there was some racial conflict between her families, since her Puerto Rican father had a light complexion as opposed to her darker skinned Dominican mother.

[14] 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 has had notable roles in other successful films, including Letty in The Fast and the Furious (2001) and Rain Ocampo in Resident Evil (2002).

In 2009, Rodriguez starred in Trópico de Sangre, an independent film based on the Dominican Republic's historic Mirabal sisters.

[34] As of 2013, Rodriguez stated she was working on several projects, including a family adventure film, a drug drama, and a female-oriented period piece.

[41] In late 2010, Rodriguez trained with Sea Shepherd to join the direct action activism of the marine conservation organization during Operation No Compromise.

"[48] The following year, she said in an interview that she hoped her actions would help others in a similar situation: "Maybe by me opening my big fat mouth like I usually do and stepping up and owning who I am, maybe it might inspire somebody else to do the same.

[53] She went to jail for 48 hours, performed community service at the morgues of two New York hospitals, completed a three-month alcohol program, and was placed on probation for three years.

[54] In 2005, while filming Lost in Hawaii, Rodriguez was pulled over by Honolulu police multiple times for speeding violations, and on December 1 was arrested for DUI.

[55][56] In April 2006, she pleaded guilty to one charge of driving under the influence, and chose to pay a US$500 fine and spend five days in jail.