The move comes after MEC for Local Government and Housing Humphrey Mmemezi resigned last week.
"Following the resignation of Humphrey Mmemezi as the MEC for Local Government and Housing, we have taken the opportunity to reflect on the overall performance of the province, including its strengths and challenges.
"In order to consolidate our position, I have decided to bolster the Executive Council by assigning new and existing members to various portfolios," she explained.
Health MEC Ntombi Mekgwe is now the MEC for Local Government and Housing with immediate effect, while the MEC for Economic Development Qedani Mahlangu is now the MEC for Infrastructure Development.
The new MEC for Health Hope Papo and Economic Development MEC Nkosiphendule Kolisile were sworn in on Monday.
Infrastructure Development MEC Bheki Nkosi will now be the head of the Gauteng Gambling Board.
Mokonyane is expected to announce the appointment of a Director-General in the Office of the Premier.
She welcomed the MECs to the positions, saying she was confident that all the new appointees would make a positive contribution to their new portfolios.
Meanwhile, the Premier expressed her joy at the appointment of Home Affairs Minister Nkosazana Dlamini Zuma as the chairperson of the African Union Commission.
"I'm on cloud nine, I'm very excited... the most important thing is that, notwithstanding the fact that... she is a woman, Comrade Nkosazana is a cadre in her own right who can compete equally on merit with anybody in terms of responsibilities," she added.
Mokonyane called on Africa to embrace Dlamini Zuma's appointment and give her the necessary support.