She has also had notable supporting roles in For Your Consideration (2006), The Hangover (2009), Bad Words (2013), Night at the Museum: Secret of the Tomb (2014), Old Dads (2023), and Mother of the Bride (2024).

In television, Harris has had main cast roles as Cooper on the ABC sitcom Notes from the Underbelly (2007–2008), Joanne Dunlevy on the Fox sitcom Surviving Jack (2014), Dr. Linda Martin on the Fox and Netflix fantasy series Lucifer (2016–2021), and Nora on season 1 of the Disney+ and Hulu horror series Goosebumps (2023).

A professor at the college recommended Harris do comedy instead of dramas but at first she did not agree with the suggestion as her intent was to be a stage actress.

[2] Harris' first acting job during college was in Cincinnati on the showboat Majestic, playing Maria from The Sound of Music.

In 2002 Harris made an appearance on Friends, I Love the '80s, and had TV commercial work which included ads for Avis and GEICO.

[7] In 2004 Harris hosted The Smoking Gun, made multiple appearances on such VH1 documentaries as I Love the '90s, Best Week Ever, The West Wing, Curb Your Enthusiasm, and an Expedia commercial.

[6][2] Harris played the supporting role of Kevyn Shecket, Kirstie Alley's personal makeup artist, on the Showtime series Fat Actress in 2005.

[10] Harris had guest roles on The Sarah Silverman Program in 2007 and 2008 and played Cooper in the ABC sitcom Notes from the Underbelly from 2007-2010.

In 2009 Harris had a role in the comedy The Hangover, playing Melissa, the domineering, abusive girlfriend to Ed Helms's character Stu.

[12] In 2010 she was in The Good Guys, a Super Bowl commercial for the 2010 Census,[13] and Off-Broadway, she performed in Love, Loss, and What I Wore.

On ABC, she made a guest appearance in the Modern Family 2011 episode "Caught in the Act" as Amelia, a restaurateur and mother to a playmate of Lily Pritchett.