When apartheid ended in 1994, Mayathula-Khoza was elected to represent the ANC as a
councillor in
Johannesburg. She was later elected as Mayor of Soweto in 1997 and as inaugural Speaker of the
City of Johannesburg council in 2000. She chaired the board of
Rand Water for four years. and newly elected Premier
David Makhura appointed her MEC for Infrastructure Development in his new Executive Council. On 2 February 2016, Makhura announced a
reshuffle in which Mayathula-Khoza was moved to the social development portfolio. Mayathula-Khoza did not seek re-election to the provincial legislature in the
2019 general election; she said that she intended to leave government to complete a
Master's degree and establish a charitable foundation, although she remained active in her local ANC branch, Gauteng's Mzala branch. In May 2021, she was appointed chairperson of the board of the
Central Drug Authority. == Personal life ==