Dunst transitioned to leading roles in teen films of 1999, the satires Dick and Drop Dead Gorgeous and Sofia Coppola’s drama The Virgin Suicides.

[12] Dunst's breakthrough role came in 1994, in the horror drama Interview with the Vampire opposite Tom Cruise and Brad Pitt, based on Anne Rice's novel of the same name.

Roger Ebert considered her portrayal of Claudia to be one of the "creepier" aspects of the film, and took note of how well she had conveyed the impression of great age inside apparent youth.

[28] She also starred in Sarah Kernochan's period comedy All I Wanna Do (1998), playing a student at an all girls' boarding school in the 1960s, opposite Gaby Hoffmann, Rachael Leigh Cook, and Lynn Redgrave.

[29] Writing for The New York Times, A. O. Scott opined that "the film is surprisingly pleasant, thanks to smart, unstereotyped performances—especially by Hoffmann and Dunst—and the filmmaker's evident respect and affection for her characters".

[30] Dunst starred in Drop Dead Gorgeous, a 1999 American satirical black comedy mockumentary film about a small town beauty pageant with Ellen Barkin and Allison Janney.

"[15] Dunst co-starred in the comedy film Dick, opposite Michelle Williams; it is a parody which retells the events of the Watergate scandal that led to the resignation of former United States president Richard Nixon.

In his review, A. O. Scott called her "a terrific comic actress, largely because of her great expressive range, and the nimbleness with which she can shift from anxiety to aggression to genuine hurt".

Charles Taylor of Salon noted that "among contemporary teenage actresses, Dunst has become the sunniest imaginable parodist", even though he thought the film had failed to provide her with as good a role as she had in either Dick or in The Virgin Suicides.

Roger Ebert of the Chicago Sun-Times wrote, "Crazy/Beautiful […] is an unusually observant film about adolescence," and "because of the real conviction that Dunst and Hernandez bring to the roles, we care about them as people, not case studies.

[47] Writing for the Los Angeles Times, Kenneth Turan reviewed that Dunst and Maguire made a real connection onscreen, concluding that their relationship "involved audiences to an extent rarely seen in films".

[25] Dunst next co-starred with Billy Bob Thornton, Morgan Freeman and Holly Hunter in the drama Levity (2003), a story of a man who is released on parole and returns to his hometown seeking redemption.

[52] Dunst co-starred as Mary Svevo opposite Jim Carrey, Kate Winslet and Tom Wilkinson in Michel Gondry's science fiction romantic comedy-drama Eternal Sunshine of the Spotless Mind (2004).

[62] In Dunst's sole project of 2005, she co-starred opposite Orlando Bloom in Cameron Crowe's romantic tragicomedy Elizabethtown as flight attendant Claire Colburn.

[75][76] Dunst's next role was in 2008, in which she co-starred opposite Simon Pegg in the comedy How to Lose Friends & Alienate People,[77] based on former Vanity Fair contributing editor Toby Young's memoir of the same name.

[82][83] She co-starred opposite Ryan Gosling in the mystery drama All Good Things (2010), based on the true story of New York real estate developer Robert Durst, whose wife disappeared in 1982.

[85][25] The critic Roger Ebert praised Dunst for her ability to capture "a woman at a loss to understand who her husband really is, and what the true nature of his family involves".

[95] Described as a Romeo and Juliet story, Peter Howell of the Toronto Star opined that there was no character development and Dunst "brings competence but no passion to her underwritten roles".

[97] Next, she had a role in Leslye Headland's romantic comedy Bachelorette (2012), starring Isla Fisher, Rebel Wilson and Lizzy Caplan; the film was produced by Will Ferrell and Adam McKay.

[101] Writing for Time magazine, Richard Corliss compared On the Road to "a diorama in a Kerouac museum ... [the film] lacks the novel's exuberant syncopation", but praises Dunst's performance.

Garnering mostly favorable reviews, the Los Angeles Times complimented the 1960s Greek setting and observed Dunst "brings a potent complexity to Colette; every mood shift registers to the bone".

[103] Jake Wilson of The Sydney Morning Herald praised the script for "condensing the book's plot while retaining its spirit", although he thought there was some uneven editing.

Dunst's portrayal of a white supervisor drew praise from Slant Magazine's Elise Nakhnikian,[110] while The Guardian thought the film was educational and entertaining despite its underdeveloped supporting cast.

[115] In that year, Dunst planned to direct an adaptation of Sylvia Plath's novel The Bell Jar, starring Dakota Fanning,[116][117] but stepped down from the project before production.

She starred alongside Colin Farrell, Nicole Kidman and Elle Fanning in the drama The Beguiled, which marked her third collaboration with Sofia Coppola, who wrote and directed the film.

It is a remake of Don Siegel's 1971 film of the same name about a wounded Union soldier who seeks shelter at an all-girls' school in the Confederate States of America.

[120] Matthew Norman of the Evening Standard similarly took note of the "impeccable" acting performances and wrote, "Dunst lends the ideal measure of coiled physical longing to her prim spinster".

Club acknowledged the "sophisticated" cinematography but thought "Character development and motivation are practically nonexistent, and the already-thin plot pushes ambiguity to the point of incoherence".

[125] Variety's Guy Lodge shared a similar opinion with the character, writing "Dunst has form in playing irretrievably inverted depression to riveting effect, but the Mulleavys' script hardly gives her as complex an emotional or intellectual palette to work with".

[132] Dunst co-starred with her partner Jesse Plemons in Jane Campion's film The Power of the Dog distributed by Netflix, and given a limited theatrical release in the USA on November 17, 2021.