She achieved wider recognition for playing the dual roles of Niki Sanders and Tracy Strauss on the NBC science fiction drama Heroes (2006–2010),[3][4] and for portraying the video game heroine Claire Redfield in the Resident Evil film series (2007–2016).

[12] Larter subsequently skipped her senior year to model in Australia, Italy, and Japan,[12] the latter a country she would temporarily settle in at the age of seventeen.

[18] In 1999, Larter made her film debut in the coming-of-age dramedy Varsity Blues, which re-united her with Dawson's Creek star James Van Der Beek and close friend Amy Smart.

Also starring Devon Sawa and Kerr Smith, the movie's premise followed several teenagers who survive a plane crash but are stalked and killed by Death itself.

[23] Directed by Les Mayfield and co-starring Colin Farrell and Scott Caan, the film was poorly received by critics[24] and at the box office, garnering US$13 million at the end of its theatrical run.

That year, Larter appeared on the cover of Maxim magazine and performed in the stage play The Vagina Monologues in New York City.

After doing so, Larter commented about future producing endeavors during an interview for Resident Evil: Extinction: "I definitely have many ideas and different avenues that I want to take as my career goes on.

"[29] In 2005, Larter appeared in the independent political thriller Confess, and had a role in the romantic comedy A Lot Like Love, starring Amanda Peet and Ashton Kutcher.

"[31] As of the third season, Larter began to play the new character of Tracy Strauss, who possessed the ability to freeze objects; and later, turn her body into water.

[33] In an interview with the BBC, Larter remarked this role was "an opportunity to overcome my fear of singing and dancing because I have no professional training [...] I really focused on the character and loved this journey she went on and the experiences she had.

[35] In 2007, she appeared opposite Milla Jovovich in Resident Evil: Extinction, portraying the character of Claire Redfield, who in the film, is the leader of a convoy of zombie apocalypse survivors who go to Alaska in search of a safe haven.

[36] The film follows an office executive (Elba) whose marriage to Knowles' character is threatened by the aggressive interests of a co-worker, portrayed by Larter.

[37] Derek Malcolm of The London Evening Standard felt that the movie was a "dim reworking of Fatal Attraction" and noted: "Larter as the pathological minx is the best thing about it.

[40] Larter reprised her role of Claire Redfield in Resident Evil: Afterlife (2010), which was filmed in 3D and saw her character ambushed and mentally manipulated by the fictional Umbrella Corporation, before she is rescued by Alice (Milla Jovovich).

[41][42][43] Like the previous Resident Evil entries, the film received negative reviews but became a major commercial success, earning US$296 million worldwide.

Larter returned to the big screen playing the love interest of a successful but psychotic man (Matt LeBlanc) in the comedy Lovesick (2014).

She portrayed the "fair-weather" friend of a woman with ALS in the independent drama You're Not You (2014), directed by George C. Wolfe and starring Hilary Swank, Emmy Rossum and Josh Duhamel.

The film received largely mixed reviews; Gary Goldstein of Los Angeles Times felt that her "fraught, more seemingly complex [character] remains underdeveloped" in what he described as a "weak horror-thriller".

[51] Larter starred in Resident Evil: The Final Chapter (2016), where her role of Claire teams up with Alice (Jovovich) and the Red Queen to save the remnants of humanity.

[52] Despite a largely mixed critical response,[53][54] with a worldwide gross of over US$312 million,[55] the film emerged as her biggest box office success.

She next starred in the thriller The Man in the White Van, which premiered at the 2023 Newport Beach Film Festival and was released in December 2024 to mixed reviews.

[10] The magazine, which billed Coleman as the movies' next dream girl, told of Allegra's relationship with David Schwimmer, how Quentin Tarantino broke up with Mira Sorvino to date her, and how Woody Allen overhauled a film to give her a starring role.

When the magazine was published, Esquire received hundreds of phone calls about the non-existent Coleman and various talent agencies sought to represent her, even after the hoax was revealed.

It has been referenced a number of times in the media[45][65][66] including on MTV's Jersey Shore, where one character refers to it as the "Varsity Blues outfit".

[69] In 2009, Larter was named Cosmopolitan magazine's Fun Fearless Female of the year at a ceremony held in Beverly Hills.

[70] Larter has appeared on the cover of numerous magazines, including (in alphabetical order) Allure, Cosmopolitan (France, Indonesia, Ecuador, Germany, Greece, Turkey and U.S.), Entertainment Weekly, Esquire, Glamour, Health, InStyle, Lucky, Maxim, Philadelphia Style, Self, Seventeen, and Shape.