Her film career began with a small part in "I Love You, I Love You Not," followed by a turn as the daughter of a New York police officer (Harrison Ford) in the thriller "The Devil's Own" (both 1997). After developing her own script at the Sundance Institute's Screenwriters Lab, Stiles offered a strong supporting performance as Phoebe, a young girl coping with an abusive home, in the Oprah Winfrey-produced "Before Women Had Wings" (ABC, 1997). While her character was peripheral, she made the most of the part as the ambivalent older sister of an innocent and trusting girl (Tina Majorino), both of whom suffer at the hands of their mother (Ellen Barkin). She went on to play the featured role of Kate Herlihy, a teenager who finds herself caught up in the social upheaval of the time, in the NBC historical miniseries "The 60s" (1999).

Stiles returned to the big screen in the leading role of Kat, a strong-willed and dauntless high school student romanced by a hired beau (Heath Ledger) who inevitably falls for her in "10 Things I Hate About You" (1999), a modern adaptation of Shakespeare's comedy "The Taming of the Shrew". Rarely cast as innocent, enthusiastic golden girls due to her self-described "New York City guard", she capably handled the challenge of presenting Kat as staunch and outspoken while still making her an accessible and likable character. Co-starring with Freddie Prize Jr. in the disappointing romance "Down to You" (2000) did little to further Stiles' career, but the feature did at least give her an opportunity to play a college student rather than a high school student. "Hamlet" (2000), another Shakespeare adaptation, found the actress playing the unhinged Ophelia opposite Ethan Hawke's take on the title character. It soon began to seem as if none of the Bard's work could be modernized without her participation in a prime role when she was cast as Desi in "O" (2001), a retelling of "Othello" set in a prep school, starring Mekhi Phifer and Josh Hartnett. Filmed in 1999 but not released theatrically until 2001 thanks to its theme of teen violence and the rash of real-life incidents, "O" was somewhat lost in the shuffle despite its powerful storytelling and strong performances.

In between, Stiles squeezed in a turn as a calculating teen out to seduce a movie star in David Mamet's "State and Main" (2000) and portrayed an aspiring ballerina who falls in love with a black student in "Save the Last Dance" (2001). The latter, a dance-fueled teen romance that somewhat captured the charm of its popular predecessors (like "Flashdance" and "Dirty Dancing"), "Save the Last Dance" hit the top of the box-office charts and helped to expose the young performer to a wider audience. Stiles went on to her most mature role up to that point in the controversial independent "The Business of Strangers", cast opposite veteran Stockard Channing as an ambitious (and potentially destructive) young businesswoman. The actress turned in a bold performance as the manipulative Paula and impressed even critics who gave the film unfavorable reviews.

A featured role in Doug Liman's take on the Robert Ludlum bestseller "The Bourne Identity" would return the actress to the big screen in 2002, and she would return to play the unfortunately knowledgeable CIA functionary Nicky for the equally successful 2004 sequel "The Bourne Supremacy." She next co-starred with Jason Lee in the much lighter "A Guy Thing" (2003), as a free-spirited woman who accidentally hooks up with her cousin's fiance. Stiles then appeared opposite fellow up-and-comers Kirsten Dunst and Maggie Gyllenhaal as the '50s-era students of liberal-minded Wellesley instructor Julia Roberts in "Mona Lisa Smile" (2003). Stiles played Joan Brandwyn, a senior who finds herself torn between her best friend's (Dunst) archtraditional notion of marriage and her mentor's (Roberts) urgings to persue greater goals at Yale Law School. Next the actress slightly squandered her talents playing a role she'd long outgrown, a med school student who falls for a European royal in the predictable, teen-oriented romantic comedy "The Prince & Me" (2004), which made nary a critical or commercial ripple.