Caitlin Clarke was born Katherine Anne Clarke in Pittsburgh, the oldest of five sisters, the youngest of whom is Torie Clarke, who was the Pentagon's chief public-relations official in 2001-2003. Her family moved to Sewickley when she was ten, where her parents still lived and worked. Clarke married in December 1980 an Oxford philosophy student who became a professor in Pennsylvania. They divorced in 1985 without children.
Clarke received her B.A. in theater arts from Mount Holyoke College in 1974 and her M.F.A. from the Yale School of Drama in 1978. During her final year at Yale Clarke performed with the Yale Repertory Theater in such plays as Tales from the Vienna Woods and Christopher Durang's 'Dentity Crisis.
The first few years of Clarke's professional career were largely theatrical, apart from her role in Dragonslayer. After appearing in three Broadway plays in 1985, Clarke moved to Los Angeles for several years as a film and television actress. She returned to theater in the early 1990s, and to Broadway as Charlotte Cardoza in Titanic. During her tenure in Titanic, Clarke taught theater at P.S. 58, New York City, in 1998-9 as part of an initiative by the Broadway Theater Institute.
Clarke was diagnosed with ovarian cancer in 2000. She returned to Pittsburgh to teach drama at the University of Pittsburgh and in the Studio G program at the Pittsburgh Musical Theater's Rauh Conservatory until her death on September 9, 2004.