Cameroon will play Ivory Coast again in another World Cup qualifier as the arch rivals were drawn in the same group for the 2022 tournament to be held in Qatar.
The two countries who have previously been drawn in the same qualifying groups will also take on Mozambique in Malawi Group D of the draw held in Cairo on Tuesday.
South Africa are set to face Ghana, Zimbabwe and Ethiopia for a chance to qualify for the competition in another tricky group.
Bafana Bafana were drawn in Group G for the qualifying tournament.
African football champions Algeria, led by Riyad Mahrez, will take on Burkina Faso, Djibouti and Niger.
Other heavyweights such as Senegal, relying on 2020 African Footballer of the Year Sadio Mane, and Mohamed Salah's Egypt will take on less-fancied nations.
Madagascar, surprise quarter-finalists in last year's Africa Cup of Nations, will face the Democratic Republic of Congo.
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 in the 2022 World Cup.
African 2022 World Cup qualifying, second-round, draw:
Group A
Algeria, Burkina Faso, Niger, Djibouti
Group B
Tunisia, Zambia, Mauritania, Equatorial Guinea
Group C
Nigeria, Cape Verde, Central African Republic, Liberia
Group D
Cameroon, Ivory Coast, Mozambique, Malawi
Group E
Mali, Uganda, Kenya, Rwanda
Group F
Egypt, Gabon, Libya, Angola
Group G
Ghana, South Africa, Zimbabwe, Ethiopia
Group H
Senegal, Congo Brazzaville, Namibia, Togo
Group I
Morocco, Guinea, Guinea-Bissau, Sudan
Group J
DR Congo, Benin, Madagascar, Tanzania