The home side kickstarted the second round of the qualifiers with a tame goalless draw away to Zimbabwe on Friday.
Ghana picked up a narrow 1-0 victory over Ethiopia on home turf. Mubarak Wakaso scored the game-winning goal in the 35th minute.
That victory helped the Black Stars climb to the summit of Group G and they are the only side to have picked up maximum points in the group on matchday one. South Africa are in second spot with one point.
South Africa vs Ghana Head-to-Head
This will be the 15th meeting between the two sides and they have been evenly matched in previous games.
They each have four wins apiece while six matches in the past have ended in a share of the spoils.
Their most recent meeting came in a qualifying fixture for the 2021 Africa Cup of Nations in March 2021. Second-half goals from Mohammed Kudus and Percy Tau saw both sides share the points in a 1-1 draw.
The hosts are currently on an eight-game winning run, while Ghana have lost one of their last five games.
South Africa form guide: D-W-W-D-W
Ghana form guide: W-D-L-W-D
South Africa vs Ghana Team News
Coach Hugo Broos called up 30 players for the qualifiers against Zimbabwe and Ghana. The squad is headlined by captain Ronwen Williams, as well as Al Ahly striker Percu Tau.
The duo of Thibang Phete and Thabiso Kutumela both tested positive for COVID-19 and entered self-isolation before the trip to Zimbabwe. Mothovi Mvala passed his fitness test due to a groin injury and should retain his place in midfield.
COVID-19: Thibang Phete, Thabiso Kutumela
Coach Charles Akonnor called up 32 players to camp but the players based in England will not partake in the game against South Africa. This is due to the country being placed in the United Kingdom's 'red list' for COVID-19 protocols.
Premier League clubs agreed not to release their players for international fixtures in red zone countries. Crystal Palace man Jeffery Schlupp suffered a hamstring injury against Ethiopia but would not have made the trip to South Africa anyway.
Injuries: Mohammed Kudus, Benson Anang
South Africa vs Ghana Predicted XI
South Africa Predicted XI (4-4-2): Ronwen Wiliams (GK); Nyiko Mobbie, Runshine De Reuck, Siyanda Xulu, Thapelo Morena; Gift Links, Teboho Mokoena, Mothobi Mvala, Luther Singh; Evidence Makgopa, Percy Tau
Ghana Predicted XI (4-2-3-1): Richard Ofori (GK); Joseph Aidoo, Aleksander Djiku, Ismail Ganiyu, Gideon Mensah; Mubarak Wakaso, Idrissu Mohammed; Daniel-Kofi Kyereh, Andre Ayew, Kamal Sulemana; Yaw Yeboah
South Africa vs Ghana Prediction
The absence of several key players for Ghana means they will not be at full-strength on Monday and this plays into the hosts' favor.
Despite this, they should still do enough to leave with a point against a rebuilding South Africa side that have struggled to impress.
Prediction: South Africa 1-1 Ghana