In April 1982, Webb joined Forbidden Broadway, an Off-Broadway revue parodying musical theatre, particularly Broadway musicals. Four years later, she made her film debut in Alex Cox's Sid & Nancy (1986); she portrayed the infamous, heroin-addicted Nancy Spungen, girlfriend of punk rock singer Sid Vicious. Her performance garnered best Actress awards from the National Society of Film Critics, the Boston Film Critics and the San Francisco Film Critics. Followed were the roles of Brian Dennehy's estranged socialite girlfriend in Peter Greenaway's 1987 drama film The Belly of an Architect; a young woman from Paoli, Pennsylvania with dreams to become a successful singer in ABC's drama television series China Beach; Webb appeared in only seven episodes. Other roles include Danny DeVito's character's eccentric girlfriend in Ivan Reitman's comedy film Twins (1988), and a cameo as a woman convinced that she had been abducted by aliens in Ghostbusters II (1989). Between roles in motion pictures and television series, Webb frequently appeared in several Los Angeles based stage productions: The House of Blue Leaves, for which she won a Drama-Logue Award, and The Model Apartment; her performance earned her a Los Angeles Drama Critics Circle Award and another Drama-Logue Award.