Clunie gained international attention for her portrayal of Melanie Marcus on Showtime's series Queer as Folk (2000–2005).

[2] In 1992, Clunie made her Los Angeles stage debut in Dean Orion's A Comedy of Eros performed at the Skylight Theatre, which earned her a Drama-Logue Award for Best Actress.

In 1995, she was cast in the Academy Award-winning The Usual Suspects[6] and shortly thereafter played a supporting role in Lost & Found.

She played Melanie Marcus in the US adaptation of Queer as Folk[8] and the biology teacher, Mrs. Finch, on MTV’s Teen Wolf.

In October 2014 it was announced Clunie was expecting a child with director Bryan Singer, and in January 2015 she gave birth to their son.