| 10 Sep 21 | Qualifier        | ExpressExpress | 2 - 1 | Al-MerrikhAl-Merrikh |
| 10 Sep 21 | Qualifier        | AmazuluAmazulu | 0 - 1 | Nyasa Big BulletsNyasa Big Bul |
| 11 Sep 21 | Qualifier        | UD SongoUD Songo | 1 - 0 | AS OtohôAS Otohô |
| 11 Sep 21 | Qualifier        | Royal LeopardsRoyal Leopard | 1 - 0 | ZESCO UnitedZESCO United |
| 11 Sep 21 | Qualifier        | Jwaneng GalaxyJwaneng Galax | 2 - 0 | DFC8DFC8 |
| 11 Sep 21 | Qualifier        | G.D. Sagrada EsperançaG.D. Sagrada | 0 - 0 | FC PlatinumFC Platinum |
| 11 Sep 21 | Qualifier        | AS ArtaAS Arta | 1 - 1 | TuskerTusker |
| 11 Sep 21 | Qualifier        | BouenguidiBouenguidi | 1 - 1 | Maniema UnionManiema Union |
| 11 Sep 21 | Qualifier        | SONABELSONABEL | 0 - 1 | Stade MalienStade Malien |
| 11 Sep 21 | Qualifier        | US GNUS GN | 1 - 1 | Le Messager NgoziLe Messager N |
| 11 Sep 21 | Qualifier        | ESAE FCESAE FC | 1 - 1 | NouadhibouNouadhibou |
| 11 Sep 21 | Qualifier        | FortuneFortune | 3 - 0 | ES SétifES Sétif |
| 11 Sep 21 | Qualifier        | TeunguethTeungueth | 0 - 1 | ASEC MimosasASEC Mimosas |
| 12 Sep 21 | Qualifier        | Fasil KenemaFasil Kenema | 2 - 2 | Al-Hilal OmdurmanAl-Hilal Omdu |
| 12 Sep 21 | Qualifier        | Mogadishu CityMogadishu Cit | 0 - 0 | APRAPR |
| 12 Sep 21 | Qualifier        | Young AfricansYoung African | 0 - 1 | Rivers UnitedRivers United |
| 12 Sep 21 | Qualifier        | Akwa UnitedAkwa United | 1 - 0 | CR BelouizdadCR Belouizdad |
| 12 Sep 21 | Qualifier        | KMKM FCKMKM FC | 0 - 2 | Al-Ittihad TripoliAl-Ittihad Tr |
| 12 Sep 21 | Qualifier        | Fovu ClubFovu Club | 0 - 1 | Atlético PetróleosAtlético Petr |
| 12 Sep 21 | Qualifier        | AkonanguiAkonangui | 0 - 1 | ZanacoZanaco |
| 12 Sep 21 | Qualifier        | LPRC OilersLPRC Oilers | 1 - 0 | ASC KaraASC Kara |
| 12 Sep 21 | Qualifier        | CI KamsarCI Kamsar | - | Hearts of OakHearts of Oak |
| 17 Sep 21 | Qualifier        | Le Messager NgoziLe Messager N | 0 - 1 | US GNUS GN |
| 17 Sep 21 | Qualifier        | DFC8DFC8 | 1 - 0 | Jwaneng GalaxyJwaneng Galax |
| 17 Sep 21 | Qualifier        | Stade MalienStade Malien | 3 - 0 | SONABELSONABEL |
| 18 Sep 21 | Qualifier        | FC PlatinumFC Platinum | 0 - 0 | G.D. Sagrada EsperançaG.D. Sagrada |
| 18 Sep 21 | Qualifier        | TuskerTusker | 3 - 0 | AS ArtaAS Arta |
| 18 Sep 21 | Qualifier        | ZanacoZanaco | 1 - 0 | AkonanguiAkonangui |
| 18 Sep 21 | Qualifier        | ZESCO UnitedZESCO United | 2 - 1 | Royal LeopardsRoyal Leopard |
| 18 Sep 21 | Qualifier        | Nyasa Big BulletsNyasa Big Bul | 1 - 3 | AmazuluAmazulu |
| 18 Sep 21 | Qualifier        | Atlético PetróleosAtlético Petr | 0 - 0 | Fovu ClubFovu Club |
| 18 Sep 21 | Qualifier        | NouadhibouNouadhibou | 2 - 0 | ESAE FCESAE FC |
| 19 Sep 21 | Qualifier        | APRAPR | 2 - 1 | Mogadishu CityMogadishu Cit |
| 19 Sep 21 | Qualifier        | Maniema UnionManiema Union | 2 - 0 | BouenguidiBouenguidi |
| 19 Sep 21 | Qualifier        | AS OtohôAS Otohô | 1 - 0 | UD SongoUD Songo |
| 19 Sep 21 | Qualifier        | Al-Hilal OmdurmanAl-Hilal Omdu | 1 - 1 | Fasil KenemaFasil Kenema |
| 19 Sep 21 | Qualifier        | Rivers UnitedRivers United | 1 - 0 | Young AfricansYoung African |
| 19 Sep 21 | Qualifier        | Hearts of OakHearts of Oak | 2 - 0 | CI KamsarCI Kamsar |
| 19 Sep 21 | Qualifier        | ASC KaraASC Kara | 2 - 1 | LPRC OilersLPRC Oilers |
| 19 Sep 21 | Qualifier        | Al-Ittihad TripoliAl-Ittihad Tr | 2 - 0 | KMKM FCKMKM FC |
| 19 Sep 21 | Qualifier        | ASEC MimosasASEC Mimosas | 1 - 0 | TeunguethTeungueth |
| 19 Sep 21 | Qualifier        | Al-MerrikhAl-Merrikh | 1 - 0 | ExpressExpress |
| 19 Sep 21 | Qualifier        | CR BelouizdadCR Belouizdad | 2 - 0 | Akwa UnitedAkwa United |
| 19 Sep 21 | Qualifier        | ES SétifES Sétif | 3 - 0 | FortuneFortune |
| 15 Oct 21 | Qualifier        | AmazuluAmazulu | 0 - 0 | TP MazembeTP Mazembe |
| 16 Oct 21 | Qualifier        | TuskerTusker | 0 - 1 | Zamalek SCZamalek SC |
| 16 Oct 21 | Qualifier        | TuskerTusker | 0 - 1 | Zamalek SCZamalek SC |
| 16 Oct 21 | Qualifier        | APRAPR | 1 - 1 | Étoile Sportive du SahelÉtoile Sporti |
| 16 Oct 21 | Qualifier        | G.D. Sagrada EsperançaG.D. Sagrada | 3 - 1 | Royal LeopardsRoyal Leopard |
| 16 Oct 21 | Qualifier        | G.D. Sagrada EsperançaG.D. Sagrada | 3 - 1 | Royal LeopardsRoyal Leopard |
| 16 Oct 21 | Qualifier        | ASEC MimosasASEC Mimosas | 3 - 1 | CR BelouizdadCR Belouizdad |
| 16 Oct 21 | Qualifier        | US GNUS GN | 1 - 1 | Al Ahly SCAl Ahly SC |
| 16 Oct 21 | Qualifier        | ASEC MimosasASEC Mimosas | 3 - 1 | CR BelouizdadCR Belouizdad |
| 16 Oct 21 | Qualifier        | US GNUS GN | 1 - 1 | Al Ahly SCAl Ahly SC |
| 16 Oct 21 | Qualifier        | Al-MerrikhAl-Merrikh | 3 - 0 | ZanacoZanaco |
| 16 Oct 21 | Qualifier        | Stade MalienStade Malien | 0 - 1 | Horoya ACHoroya AC |
| 16 Oct 21 | Qualifier        | Stade MalienStade Malien | 0 - 1 | Horoya ACHoroya AC |
| 16 Oct 21 | Qualifier        | Al-MerrikhAl-Merrikh | 3 - 0 | ZanacoZanaco |
| 17 Oct 21 | Qualifier        | Jwaneng GalaxyJwaneng Galax | 0 - 2 | Simba SCSimba SC |
| 17 Oct 21 | Qualifier        | Jwaneng GalaxyJwaneng Galax | 0 - 2 | Simba SCSimba SC |
| 17 Oct 21 | Qualifier        | Maniema UnionManiema Union | 2 - 2 | Mamelodi SundownsMamelodi Sund |
| 17 Oct 21 | Qualifier        | AS OtohôAS Otohô | 2 - 2 | Atlético PetróleosAtlético Petr |
| 17 Oct 21 | Qualifier        | NouadhibouNouadhibou | 3 - 1 | ES SétifES Sétif |
| 17 Oct 21 | Qualifier        | Maniema UnionManiema Union | 2 - 2 | Mamelodi SundownsMamelodi Sund |
| 17 Oct 21 | Qualifier        | Rivers UnitedRivers United | 1 - 1 | Al-Hilal OmdurmanAl-Hilal Omdu |
| 17 Oct 21 | Qualifier        | LPRC OilersLPRC Oilers | 0 - 2 | Raja CasablancaRaja Casablan |
| 17 Oct 21 | Qualifier        | AS OtohôAS Otohô | 2 - 2 | Atlético PetróleosAtlético Petr |
| 17 Oct 21 | Qualifier        | Rivers UnitedRivers United | 1 - 1 | Al-Hilal OmdurmanAl-Hilal Omdu |
| 17 Oct 21 | Qualifier        | LPRC OilersLPRC Oilers | 0 - 2 | Raja CasablancaRaja Casablan |
| 17 Oct 21 | Qualifier        | Hearts of OakHearts of Oak | 1 - 0 | Wydad CasablancaWydad Casabla |
| 17 Oct 21 | Qualifier        | Al-Ittihad TripoliAl-Ittihad Tr | 0 - 0 | Espérance de TunisEspérance de |
| 17 Oct 21 | Qualifier        | Al-Ittihad TripoliAl-Ittihad Tr | 0 - 0 | Espérance de TunisEspérance de |
| 22 Oct 21 | Qualifier        | Zamalek SCZamalek SC | 4 - 0 | TuskerTusker |
| 23 Oct 21 | Qualifier        | ZanacoZanaco | 2 - 1 | Al-MerrikhAl-Merrikh |
| 23 Oct 21 | Qualifier        | Royal LeopardsRoyal Leopard | 1 - 0 | G.D. Sagrada EsperançaG.D. Sagrada |
| 23 Oct 21 | Qualifier        | ZanacoZanaco | 2 - 1 | Al-MerrikhAl-Merrikh |
| 23 Oct 21 | Qualifier        | Étoile Sportive du SahelÉtoile Sporti | 4 - 0 | APRAPR |
| 23 Oct 21 | Qualifier        | TP MazembeTP Mazembe | 1 - 1 | AmazuluAmazulu |
| 23 Oct 21 | Qualifier        | TP MazembeTP Mazembe | 1 - 1 | AmazuluAmazulu |
| 23 Oct 21 | Qualifier        | Atlético PetróleosAtlético Petr | 2 - 0 | AS OtohôAS Otohô |
| 23 Oct 21 | Qualifier        | Atlético PetróleosAtlético Petr | 2 - 0 | AS OtohôAS Otohô |
| 23 Oct 21 | Qualifier        | Al Ahly SCAl Ahly SC | 6 - 1 | US GNUS GN |
| 23 Oct 21 | Qualifier        | Al Ahly SCAl Ahly SC | 6 - 1 | US GNUS GN |
| 23 Oct 21 | Qualifier        | Raja CasablancaRaja Casablan | 2 - 0 | LPRC OilersLPRC Oilers |
| 23 Oct 21 | Qualifier        | Raja CasablancaRaja Casablan | 2 - 0 | LPRC OilersLPRC Oilers |
| 24 Oct 21 | Qualifier        | Simba SCSimba SC | 1 - 3 | Jwaneng GalaxyJwaneng Galax |
| 24 Oct 21 | Qualifier        | Simba SCSimba SC | 1 - 3 | Jwaneng GalaxyJwaneng Galax |
| 24 Oct 21 | Qualifier        | Mamelodi SundownsMamelodi Sund | 2 - 0 | Maniema UnionManiema Union |
| 24 Oct 21 | Qualifier        | Mamelodi SundownsMamelodi Sund | 2 - 0 | Maniema UnionManiema Union |
| 24 Oct 21 | Qualifier        | Espérance de TunisEspérance de | 1 - 0 | Al-Ittihad TripoliAl-Ittihad Tr |
| 24 Oct 21 | Qualifier        | Horoya ACHoroya AC | 2 - 1 | Stade MalienStade Malien |
| 24 Oct 21 | Qualifier        | Espérance de TunisEspérance de | 1 - 0 | Al-Ittihad TripoliAl-Ittihad Tr |
| 24 Oct 21 | Qualifier        | ES SétifES Sétif | 2 - 0 | NouadhibouNouadhibou |
| 24 Oct 21 | Qualifier        | Al-Hilal OmdurmanAl-Hilal Omdu | 1 - 0 | Rivers UnitedRivers United |
| 24 Oct 21 | Qualifier        | Horoya ACHoroya AC | 2 - 1 | Stade MalienStade Malien |
| 24 Oct 21 | Qualifier        | Al-Hilal OmdurmanAl-Hilal Omdu | 1 - 0 | Rivers UnitedRivers United |
| 24 Oct 21 | Qualifier        | ES SétifES Sétif | 2 - 0 | NouadhibouNouadhibou |
| 24 Oct 21 | Qualifier        | CR BelouizdadCR Belouizdad | 2 - 0 | ASEC MimosasASEC Mimosas |
| 24 Oct 21 | Qualifier        | CR BelouizdadCR Belouizdad | 2 - 0 | ASEC MimosasASEC Mimosas |
| 24 Oct 21 | Qualifier        | Wydad CasablancaWydad Casabla | 6 - 1 | Hearts of OakHearts of Oak |