Rachael Harris was born in Worthington, Ohio, where she spend most of her early life. In 1986, she graduated from Worthington High School. She then attended Otterbein College, a liberal arts college located in Westerville, Ohio. She graduated in 1989, with a Bachelor of Fine Arts. Harris joined the Groundlings, an improvisational and sketch comedy troupe. The troupe maintains its own school in Los Angeles, where experienced members train young performers. Harris has served as a teacher in the school.
In the 1990s, Harris made a number of appearances in American television shows, starting with single-episode roles in the science fiction series seaQuest DSV and Star Trek: Voyager. Harris had a recurring role in the sitcom Sister, Sister as Simone. Harris continued making guest appearances on television shows throughout the 2000s, and also appeared in a number of documentaries and advertisement campaigns. She appeared as a correspondent of the news satire The Daily Show for a single season (2002-2003). Harris was cast as Kevyn Shecket, a member of the supporting cast in the comedy series Fat Actress (2005).
Movie credits include the comedy film The Hangover (2009), and a recurring film role in the film series Diary of a Wimpy Kid (2010-2012), where she played Susan Heffley (the protagonist's mother).
