Barkin became a notable actress in the 1980s. Her break out role was in Barry Levinson's Diner (1982), for which she received favorable reviews. Barkin would later appear in several successful films, including the thrillers Sea of Love, opposite Al Pacino (1989), and The Big Easy (1987), opposite Dennis Quaid.

Barkin also appeared in off-Broadway plays. New York Times critic Frank Rich summarized her performance in the play, Eden Court, saying: "If it were really possible to give the kiss of life to a corpse, the actress Ellen Barkin would be the one to do it. In Eden Court, the moribund play that has brought her to the Promenade Theater, Miss Barkin is tantalizingly alive from her bouncing blond ponytail to the long legs that gyrate wildly and involuntarily every time an Elvis Presley record plays on stage".

Barkin has also done work in made-for-television films like Before Women Had Wings (1997) and The White River Kid (1999). Currently, she voices the start of each Th