Breckenridge guest starred on Freaks and Geeks in 2000 as a character named Shelly Weaver. When she was 15, she met James Franco at an audition. She was surprised that Franco recognized her on set on Freaks and Geeks. She also guest starred on Dawson's Creek, CSI, Buffy the Vampire Slayer, Charmed, Undeclared, Medium and JAG. She guest starred as Francise in three episodes of Opposite Sex. In 2002, she appeared in the film Big Fat Liar starring Frankie Muniz as Jason Shepherd's older sister Janie.

Breckenridge has had numerous voice roles on the animated television series Family Guy. During an interview with FHM, she stated quoting: “When I first went for Family Guy I auditioned for a guest voice. I don't know why but Seth MacFarlane really likes the sound of my voice. I'll never understand that. He just liked me and they call me back all the time to do different things”. Breckenridge often does celebrity impressions on the show, such as Sarah Jessica Parker and Renée Zellweger. She also had roles on MacFarlane's web series Cavalcade of Cartoon Comedy. She guest starred in the episode “With Friends Like Steve's” of American Dad!, also created by MacFarlane.

She is interested in photography and has her own darkroom in her apartment. At age 24, she began taking photography seriously as a form of self-expression. Her then-boyfriend Bryten Goss helped her with lighting. In 2008, she had her first exhibit with Shalon Goss hosted by her uncle Michael Weatherly and presented by Edgar Valera. She stated quoting: “I had so much to express emotionally with this show. Each photo is an expression of myself and the things I have gone through in the last three years. From my perspective, the purpose of art is to evoke feeling and to inspire. That's all I hope to achieve.”

In 2006, Breckenridge starred as Monique in the film She's the Man. She starred as Willa McPherson in television series Dirt from 2007 to 2008. She has appeared in a couple of shows that have later been cancelled. She does not take this personally as her roles are mostly supporting characters. In 2009, Breckenridge co-starred in the independent film The Bridge to Nowhere by Blair Underwood. She also has a role in the upcoming film Ticket Out.

Deadline reported that Brechenridge will become a recurring actress in season 4 of HBO's True Blood.