Born on Gauteng's East Rand, Mekgwe was Mayor of Nigel from 1995 to 2000 and then served as Speaker of the Ekurhuleni Metropolitan Council from 2001 to 2008.

She left the mayoral office in November 2010 when, shortly after her election as ANC Provincial Treasurer in Gauteng, she was appointed to the Executive Council of Premier Nomvula Mokonyane.

Lentheng Helen "Ntombi" Mekgwe[1][2] was born in Chatterston near Nigel on the East Rand of what is now Gauteng province.

[5] The Independent said that Mekgwe was a frontrunner in the race to replace him, although other possible contenders included Panyaza Lesufi, Vulindlela Mapekula, and Chief Whip Moses Maseko.

[10] News24 said that Mekgwe played "a critical role" at the conference in helping Mashatile to defeat a challenge to his incumbency by Nomvula Mokonyane, then the Premier of Gauteng.

Mekgwe succeeded Qedani Mahlangu as Member of the Executive Council (MEC) for Social Development and Health.

[20] Sources told the Mail & Guardian that the ANC National Executive Committee had selected Mekgwe for election as Premier: according to the newspaper, Makhura was the preferred candidate of the Mashatile-led Gauteng ANC, but Mekgwe was viewed as "a welcome compromise because of the good relationship she enjoys with top provincial leaders".

[16] In addition, in November 2021, she was elected to a three-year term as the Treasurer for the Africa region of the Commonwealth Parliamentary Association.