Born in Port Shepstone, in the province of Natal, Madikizela soon moved to Khayelitsha and became politically active in the area.

A year later, in 2015, Madikizela unseated party stalwart Theuns Botha as deputy provincial leader of the DA.

His brother helped him enrol at a computer school and Madikizela soon started studying human resource management at the University of South Africa (UNISA).

[6][7] Although he was not elected as a councillor, Madikizela remained politically active, joining the United Democratic Movement (UDM) in 2007.

The ANC called for Helen Zille to fire him, angered that he had linked the provision of services to the apartheid policy of influx control.

[14][15] In April 2015, Madikizela was elected deputy provincial leader of the Democratic Alliance in the Western Cape, unseating DA veteran Theuns Botha.

[16] He was subsequently named the acting provincial leader in February 2017, when incumbent Patricia de Lille resigned.

[17][18][19] Madikizela was appointed as Provincial Minister of Transport and Public Works by newly elected premier Alan Winde in May 2019.

[20] In October 2019, he declared his intention to run for interim Federal Leader of the DA following Mmusi Maimane's resignation.

In mid-November 2020, Madikizela was accused of plotting to assassinate his main competitor for the position, Masizole Mnqasela, the speaker of the provincial parliament.

[27] On 1 April 2021, acting Public Protector Kholeka Gcaleka released a report that found that Madikizela had violated the Executive Ethics Codes by making misleading or false statements to the legislature about Brett Herron, a Good MPP.

[28] On 6 April 2021, Madikizela announced that he had applied to be the DA's mayoral candidate for the City of Cape Town.

[29] On 13 April 2021, Daily Maverick reported that Madikizela did not have a Bachelor of Commerce degree in Human Resource Management as previously claimed and that he had misled a journalist in this regard.

[30] The next day, the DA subsequently announced that its Federal Legal Commission would investigate claims that he lied about having a BCom degree.

The appointment was not immediate, because the Department of Public Service and Administration had to first vet the application to ensure that it is in line with associated regulations.