She is best-known for her portrayal as Roo Stewart on the soap opera Home and Away (1988–1989), as Ally Kovac on the drama series Tangle (2009–2012), and as a presenter on the Australian children's show Play School, a role which she has held since 1999.

[5] Following her departure from Home and Away in 1989, Clarke appeared in the short-lived series Family and Friends before going on to act in several mini-series including Come In Spinner and Golden Fiddles.

The role of Meryl Lee in Look Both Ways scored Clarke a nomination for an Australian Film Institute (AFI) Lead Actress award in 2005.

Other television appearances followed, including playing the role of Bernadette in The Time of Our Lives from 2013 to 2014;[7] Eve in House Husbands in 2016, and as Noelene Hogan in Hoges.

[8] An experienced stage actor, Clarke has worked with the Sydney Theatre Company in productions such as A Man with Five Children, Trelawny of the Wells, Cyrano de Bergerac, The Herbal Bed, Hedda Gabler, Stiffs and Muriel's Wedding.

[12] In the 1990s, Clarke performed in a number of bands with fellow Australian thespians, including Loene Carmen and Noah Taylor.

These groups included the country and western combo The Honky Tonk Angels; punk band The White Trash Mamas; and the avant-garde Cardboard Box Man.

[13] In the late '90s she was a backing vocalist in the Sydney band Automatic Cherry, which also featured The Cruel Sea guitarist James Cruickshank.

[15] In 2016, Clarke collaborated with singer-songwriter Josh Pyke on 'Words Make The World Go Around', a song to celebrate, promote and raise funds for the work of the Indigenous Literacy Foundation.