Bafana Bafana kick-off their 2021 Africa Cup of Nations (AFCON) qualifying campaign on Thursday, November 14 in a tricky away clash to Ghana.
The last time South Africa shared the field with the Black Stars, Bafana Bafana held the west Africans to a goalless draw in an international friendly earlier this year.
Nearly seven months after that fixture, South Africa will attempt to get an all-important three points at the Cape Coast Sports Stadium.
Since readmission, Bafana have played the Black Stars on 12 occasions - 4 wins, 5 draws and 3 defeats - with the first clash dating back to November 1994.
A 15 000-strong crowd travelled to Loftus Versfeld Stadium where Ghana fielded the likes of Samuel Osei Kuffour, Abedi Pele Ayew, Frank Amankwah and Robert Sabah.
Clive Barker's South Africa beat Ghana 2-1 courtesy of goals from legendary Marks Maponyane and Theophilis Khumalo with Amankwah grabbing a late goal for the Ghanaians.
That victory was the first of four wins South Africa would get over the Black Stars.
In 1996, Bafana beat Ghana 3-0 in an AFCON semi-final with John Mosheau scoring a brace and Shaun Bartlett netting a goal to guide South Africa to the final.
Bafana were crowned AFCON champions after beating Tunisia in the final to claim their first major trophy - and sadly the national team's last.
Thursday's clash is the first step towards a possible final in 2021 where Cameroon will host the tournament.
Ghana's first win over South Africa only came in a World Cup qualifier 10-years after Bafana Bafana were granted readmission in 2004.
Sulley Muntari and Stephan Appiah were on the scoresheet as Ghana dismantled South Africa 3-0 in Kumasi.
A year later in 2005, Ghana travelled to South Africa and left with three points as Bafana Bafana failed to qualify for the World Cup in Germany.
Ghana, currently ranked 7th in Africa, are expected to once again defeat South Africa (12th) who are going into their second match under new coach Molefi Ntseki.
Ntseki's first match came in the Nelson Mandela Challenge last month against Mali in which South Africa won 2-1 courtesy of goals from Dean Furman and Themba Zwane.
The 50-year-old has recently stated that he hopes Bafana Bafana can hold their nerve and grind out a positive result.
Kick-off is at 21:00 on Thursday evening (SA time).
Darren Keet (Leuven, Belgium), Ronwen Williams (SuperSport United), Ricardo Goss (Bidvest Wits)
Midfielders
Lebo Mothiba (Strasbourg, France), Bradley Grobler (SuperSport United), Kermit Erasmus (CT City) Thembinkosi Lorch (Orlando Pirates), Percy Tau (Club Brugge, Belgium)
GHANA SQUAD:
Goalkeepers
Richard Ofori (Maritzburg FC, South Africa), Felix Annan (Asante Kotoko, Ghana), Razak Abalora (Azam FC, Tanzania)
Defenders
Andy Yiadom (Reading, England), Harrison Afful (Columbus Crew, USA), Lumor Agbenyenu (Real Mallorca, Spain), Joseph Aidoo (Celta Vigo, Spain), Kassim Nuhu (Fortuna Dusseldorf, Germany), Nicholas Opoku (Udinese, Italy), Mohammed Salisu (Real Valladolid, Spain)
Midfielders
Samuel Owusu (Al Fahya, Saudi Arabia), Thomas Partey (Atletico Madrid, Spain), Alfred Duncan (Sassuolo, Italy), Mubarak Wakaso (Deportivo Alaves, Spain), Iddrisu Baba (Real Mallorca, Spain), Christopher Antwi-Adjei (SC Paderborn, Germany)
Forwards
Andre Ayew (Swansea, England), Mohammed Kudus (FC Nordsjaelland, Denmark), Emmanuel Boateng (Dalian Yifang, China), Jordan Ayew (Crystal Palace, England), Torric Jibril (TP Mazembe, DR Congo), Shafiu Mumuni (Ashantigold)