Ellen Cleghorne was raised in the projects of Brooklyn, and after earning a degree at Hunter College on Manhattan's Upper East Side, began performing standup in clubs throughout New York City. She also performed with "The Family, Inc.", a troupe which performed mainly at prisons, and appeared in two productions with the New York Shakespeare Festival, "Marriage Proposal," and "Looking for Tomorrow." Although she had been featured on several episodes of Keenen Ivory Wayans' variety series "In Living Color" (Fox) in the early 1990s, Cleghorne was noticed by the producers of "Saturday Night Live" while performing at a New York comedy club and was asked to join the show in 1991. During the course of four seasons, she only created original characters, but offered dead-on impersonations of Anita Hill, Whoopi Goldberg, and singer Natalie Cole, among others. She withdrew from "SNL" to headline her own sitcom, the short-lived "Cleghorne" (1995-96), playing a single mother coping with daily life on the fledgling new network, The WB.
Cleghorne's work in feature films was slower in getting established. She made a quick appearance in "Turk 182" (1985), but did not have a part of substance until Nora Ephron's "This is My Life" (1992), as a talk show host. She also had a supporting role in the Ellen DeGeneres vehicle "Mr. Wrong" (1996).