Maria Bamford started doing stand-up in Minneapolis, Minnesota, at the age of 19 at Stevie Ray's Comedy Cabaret and later joined Edinburgh's improvised comedy show The Improverts.

She has been in a number of movies and television shows, including several voice appearances in cartoons. One of the best-known aspects of Bamford's act is the many different voices she uses.

Her comedy often takes the form of vignettes rather than the standard setup/punchline format. Because her stage voice has been described as child-like, her various impersonations contrast sharply and draw a reaction from the audience as they sound more adult.