In 1993, Clarke featured prominently in the music video "For Tomorrow" for the British band Blur.
From 2018 to 2022, Clarke played the role of Aunt Sarah in the Channel 4 sitcom Derry Girls written by Lisa McGee.
[5][6] In 2020, Clarke played the role of Sybil Stamfordis in the BBC One miniseries, The Pale Horse.
Ann Donahue, writing for IndieWire, said that Clark's "portrayal of witch Sybil is a fun triple-take-inducing switch from her work as the ditzy aunt on Derry Girls.
Clarke has also appeared on stage and has appeared in shows such as Brilliant Traces, Low Level Panic, The Coronation Voyage, Woman and Scarecrow, Scarborough, God of Carnage, Macbeth, Primecut, The Recruiting Office, Heartbreak House, Hamlet, Pentecost, Spokesong, The Bonefire, Dream of Autumn, Attempts on her Life, Don Carlos, Roberto Zucco, Shining City, Faith Healer, Lagan, Borders of Paradise, Torquato Tasso, Once a Catholic, The Factory Girls, Jekyll and Hyde, Riders to the Sea, Damaged Goods, Summit Conference, Medea, Stormont: a Farce and An Oak Tree.