Garofalo officially began her career in stand-up comedy in the late 1980s during the pre-grunge era. Her appearance was often in line with late 1980s style: disheveled with thick black glasses and unkempt hair. Her comedy is often self-deprecating; she has made fun of popular culture and the pressures on women to conform to body image ideals promoted by the media. Garofalo's comedy shows involve her and her notebook, which is filled with years' worth of article clippings and random observations she references for direct quotes during her act. Garofalo has said that she does not tell jokes as much as make observations designed to get laughs. She was part of the alternative comedy scene in Los Angeles in the early 1990s, appearing at Un-Cabaret and other venues.
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