A member of the Democratic Alliance, Clarke served as a councillor in the Ekurhuleni Metropolitan Municipality from 2004 until her election to the Gauteng Provincial Legislature as a DA representative in 2014.

After serving one term in the provincial legislature, Clarke was elected to the National Assembly of South Africa in 2019.

On 5 June 2019, the DA parliamentary leader, Mmusi Maimane, appointed her as Shadow Deputy Minister of Public Service and Administration.

[3] On 5 December 2020, Clarke was appointed as Shadow Deputy Minister of Public Enterprises by John Steenhuisen.

[3] By February 2022, Clarke had been promoted to Shadow Minister of Health, succeeding Siviwe Gwarube, who left the position after she was elected deputy chief whip of the DA caucus in December 2021.