Judy Tenuta's comic persona is excessively self-aggrandizing to the point of megalomania and deems herself to be "A Goddess" among other things. She is also noted for using abrupt changes in mood or vocal pitch and for her accordion. In recent years she might be most known for her work with "Weird Al" Yankovic and appearances on Hollywood Squares.

Her use of voice in her act perhaps lent itself to voice-over work and hence she has been in several animated programs. This includes doing the voice of Edna on Duckman, Black Widow on Space Ghost Coast to Coast, and as herself in Dr. Katz, Professional Therapist. Besides animation she also had a role on The Weird Al Show.