Formerly an anti-apartheid activist in the United Democratic Front, Mashatile was a member of President Jacob Zuma's first cabinet, serving as Minister of Arts and Culture from 2010 to 2014.

[1][6][7] When the apartheid government unbanned the African National Congress (ANC) and South African Communist Party (SACP) in 1990, Mashatile was recruited to the interim leadership corps of both organisations and tasked with helping establish their new legal structures inside the country and especially in the PWV region that later became Gauteng, then led by trade unionist Kgalema Motlanthe.

[5][6][8] As Finance MEC, he was closely involved in planning the Gautrain rapid-transit project,[10][5] and also formulated and established the Gauteng Shared Services Centre, which centralised the budget allocations of provincial departments and which has been criticised as inefficient and vulnerable to corrupt abuses.

[3][14][17] At the conference, which opened in Midrand on 7 October 2007, outgoing Provincial Chairperson Shilowa declined a nomination to stand for re-election; he was rumoured to support Mashatile's bid to succeed him.

[19] On 7 October 2008, Mashatile was elected Gauteng Premier, replacing Shilowa, who had resigned in protest against the ANC's decision to remove President Thabo Mbeki from office.

This was viewed as a "slap in the face" for Mashatile, given his popularity in the province and ANC norms about reserving premierships for provincial party chairpersons.

[8][21][22] In subsequent months, the Sowetan reported that Mashatile faced division inside the provincial ANC, with some groups aligned to Mokonyane or the Motshekgas.

[43][44] He left the national legislature in February 2016, when he was appointed MEC for Human Settlements and Cooperative Governance in the cabinet of Gauteng Premier David Makhura, a close ally.

[51] On 18 December 2017, Mashatile was elected Treasurer General of the ANC at the latter's 54th National Conference, which also marked the end of Zuma's term as party president.

With some pundits believing Mashatile would be a better Deputy President than his predecessor, David Mabuza who had been notorious for long absenteeism from official government and public events.

[64] [65] On March 2024, Mashatile stood in for President Ramaphosa by attending the Proudly South African Presidential Localization Dinner at the Sandton Convention Centre in Johannesburg.

[66] Mashatile made a trip to the United Kingdom, to meet with high level government officials, executives of big corporations as well as SMMEs and start-ups.

[67] Mashatile has frequently been identified as a leading member of the so-called "Alex mafia" – a term whose use was banned in the Gauteng legislature in 2010,[68] and which refers to a network of politicians and businesspeople with personal ties originating in Alexandra township's anti-apartheid movement.

[69] In 2006, the Mail & Guardian reported that such ties might have led Mashatile to acquire shares in a software company with state contracts, possibly creating a conflict of interest.

[10] Two months later, Mashatile hosted another government dinner at the same restaurant, at a higher cost of R108,000, and his spokesperson inflamed the scandal by falsely denying the reports.

[76] In an ensuing investigation, the Gauteng Integrity Commissioner again cleared Mashatile, this time of allegations that he had misused his government credit card or fraudulently under-reported his expenditures.

[77] Ahead of the 2019 general election, controversy arose around claims that the Gauteng government had wasted – or its politicians pilfered – R1.3 billion in funds intended for the Alexandra Renewal Project, a welfare scheme coordinated by Mashatile's department during his first term as Human Settlements MEC (1999–2004).

In the course of a joint inquiry by the Public Protector and South African Human Rights Commission, Mashatile and other officials denied that any such amount had gone missing or been allocated in the first place.

[78] Mashatile filed a R2-million defamation lawsuit against opposition party the Economic Freedom Fighters and two of its leaders, Julius Malema and Mandisa Mashego,[79][80] after they implied that he had been involved in corruption in administering the Alexandra Renewal Project.