A photogenic former singer for pop group Blondie who demonstrated a degree of acting talent in "Union City" (1980) and David Cronenberg's "Videodrome" (1983), Harry has also performed the theme songs for several films, and provided the songs for others. After completing junior college, Harry headed to New York City where, in the late 60s, she was a back-up singer for the group The Wind in the Willows. In 1974, while performing with the cabaret troupe The Stilettoes, she met Chris Stein and together they founded the rock group Blondie with Harry as lead singer. Hits such as "Heart of Glass" (1979) and "Call Me" (1980, featured in Paul Schrader's "American Gigolo") followed, and Harry won an ASCAP Award for writing the former. Blondie became one of the leading rock bands of the late 70s and into the 80s. The group's songs were heard on the soundtrack of "Little Darlings" (1980), Harry wrote the title song for "Polyester" (1981) and performed a song specifically for "Rock & Rule" (1982). Harry made her TV debut singing on "Music Central", a 1981 syndicated program, and Blondie had its own HBO special in 1983.
But Harry also had intentions of launching an acting career. She first appeared on film in 1978 with a small role in "The Foreigner," and played herself in "Roadie" (1980). But her first chance to really prove her mettle came with "Union City", a quirky independent film in which Harry was the wife of a neurotic businessman who beats a vagrant to death. Harry came away with good notices, and added her off-centered presence to "Videodrome" before playing the title role in "Forever, Lulu" (1987), although she only had a brief cameo appearance. Harry had a larger role for director John Waters in "Hairspray" (1988), in which she was Velma Von Tussle, the wife of another rock icon, Sonny Bono, and a demanding (although racist) stage mother driving her daughter to win the "Miss Auto Show" contest. Harry also had a quick part in "New York Stories" (1989). In James Mangold's "Heavy" (1996), she won praise for her portrayal of a world-weary waitress who embodies the ennui of the small town in which the film is set.
Her TV appearances have been sporadic. Harry had a recurring role in a 1989 storyline of the CBS series "Wiseguy" that focused on corruption in the music industry. She made her TV-movie debut playing a woman who sells phone sex and becomes the target of a serial killer in "Intimate Strangers" (Showtime, 1991). Harry also provided the voice of Vaingloria for the syndicated animated series "Phantom 2040" from 1994-96.