While studying, Rauch did stand-up comedy around Manhattan and soon made a name for herself on the New York City comedy scene. Her critically acclaimed one-woman show The Miss Education of Jenna Bush, in which she portrayed the former President's daughter, played to sold-out audiences.
In 2009 Rauch began playing the recurring role of Bernadette, the girlfriend of Howard Wolowitz, in the third season of TV's The Big Bang Theory. The following season her character became Howard's fiancée and Rauch was promoted to a series regular. The characters married in the season five finale. In December 2011, Rauch was nominated as part of The Big Bang Theory cast for the Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Comedy Series.
Rauch has been a participant in VH1's Best Week Ever television show. Other acting credits include True Blood, on which she had a recurring role in 2010 as Summer, a girl who likes Hoyt, and The Office. Rauch also appeared on the American remake of the Australian TV series Kath & Kim. She also appeared in Wright v Wrong, Dirty Sexy Money, and in the film I Love You, Man.