South Africa are set to face Ghana, Zimbabwe and Ethiopia for a chance to qualify for the 2022 World Cup.
Bafana Bafana were drawn in Group G for the qualifying tournament.
African football champions Algeria will take on Burkina Faso, Djibouti and Niger.
Other heavyweights such as Senegal and Egypt will take on less-fancied nations.
All five African teams failed to reach the knockout stage of the 2018 World Cup, the first time that had happened since 1982.
Forty teams will compete in 10 groups after the draw in Cairo.
Winners from the first round join 26 top-seeded sides based on FIFA's world rankings.
The matches will take place from March 2020 until October 2021.
Group winners will advance to the third round, which will be played in November 2021. The five winners of the final round will secure berths at the 2022 World Cup.