The Black Stars of Ghana will play the second Group C game against São Tomé and Príncipe today, Monday, November 18 at the Estadio Nacional 12 de Julho.
The four-time African champions made a strong start to their qualifying campaign for the 2021 finals with a 2-0 win against South Africa on Thursday at the Cape Coast stadium.
Atletico Madrid midfielder, Thomas Partey opened the scoring in the first half and substitute Kudus Mohammed celebrated his first cap by finding the net late on in the second to see off the challenge of South Africa.
Ghana will be expecting to leave with nothing less than three points as they have an excellent record in AFCON qualifying with only two defeats from their last 26 qualifying games.
However, Sao Tome & Principe have never qualified for the AFCON finals and opened their 2021 qualifying group stage campaign with a comprehensive 4-0 defeat away from home against Sudan.
Sao Tome conceded the opening goal in the eighth minute so were already 1-0 down when they were reduced to 10 men in the 21st minute after midfielder Aldaire Santos was sent-off and thereafter they never looked likely to salvage anything from the match.
Although competitive wins are rare for Sao Tome they won their last competitive home match, a 2-1 victory against Mauritius in the 2021 Africa Cup of Nations qualification preliminary round last month.
Kwesi Appiah and his lads trained at the Madina Zurak Park on Friday and Saturday before jetting to Sao Tome on Sunday.
The match has been scheduled to start at 13:00GMT.
Richard Ofori, Andy Yiadom, Gideon Mensah, Joseph Aidoo, Kassim Nuhu, Iddrisu Baba, Andre Ayew (C), Thomas Partey, Alfred Duncan, Jordan Ayew, Kudus Mohammed