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| 1st(1st leg) | Butrinti Sarandë | - | KF Laçi | 1:1 | ||
| 2nd (2nd leg) | KF Laçi | - | Butrinti Sarandë | 4:0 | ||
| 1st(1st leg): 22/09/2021 12:30 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: KF Laçi | ||||
| 1st(1st leg) | KS Besa | - | KS Pogradeci | 1:0 | ||
| 2nd (2nd leg) | KS Pogradeci | - | KS Besa | 2:0 | ||
| 1st(1st leg): 22/09/2021 13:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: KS Pogradeci | ||||
| 1st(1st leg) | KF Tërbuni Pukë | - | FK Partizani | 0:3 | ||
| 2nd (2nd leg) | FK Partizani | - | KF Tërbuni Pukë | 3:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: FK Partizani | ||||
| 1st(1st leg) | KS Shkumbini | - | KF Tiranë | 0:3 | ||
| 2nd (2nd leg) | KF Tiranë | - | KS Shkumbini | 6:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: KF Tiranë | ||||
| 1st(1st leg) | KF Veleçiku Koplik | - | KF Skënderbeu | 0:3 | ||
| 2nd (2nd leg) | KF Skënderbeu | - | KF Veleçiku Koplik | 4:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: KF Skënderbeu | ||||
| 1st(1st leg) | KF Oriku | - | KF Bylis Ballsh | 1:2 | ||
| 2nd (2nd leg) | KF Bylis Ballsh | - | KF Oriku | 4:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 14/10/2021 12:30 | Winner: KF Bylis Ballsh | ||||
| 1st(1st leg) | Erzeni Shijak | - | Dinamo Tiranë | 1:0 | ||
| 2nd (2nd leg) | Dinamo Tiranë | - | Erzeni Shijak | 2:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 14/10/2021 12:30 | Winner: Dinamo Tiranë | ||||
| 1st(1st leg) | KS Besëlidhja Lezhë | - | KS Burreli | 0:0 | ||
| 2nd (2nd leg) | KS Burreli | - | KS Besëlidhja Lezhë | 2:4 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 14/10/2021 12:30 | Winner: KS Besëlidhja Lezhë | ||||
| 1st(1st leg) | FK Vora | - | KS Korabi Peshkopi | 2:1 | ||
| 2nd (2nd leg) | KS Korabi Peshkopi | - | FK Vora | 4:1 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: KS Korabi Peshkopi | ||||
| 1st(1st leg) | KF Maliqi | - | FK Kukësi | 0:0 | ||
| 2nd (2nd leg) | FK Kukësi | - | KF Maliqi | 4:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: FK Kukësi | ||||
| 1st(1st leg) | KF Elbasani | - | KS Kastrioti | 0:2 | ||
| 2nd (2nd leg) | KS Kastrioti | - | KF Elbasani | 2:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: KS Kastrioti | ||||
| 1st(1st leg) | Flamurtari Vlorë | - | KF Apolonia Fier | 1:1 | ||
| 2nd (2nd leg) | KF Apolonia Fier | - | Flamurtari Vlorë | 5:6 (1:0, 1:1, 1:1) pso | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: Flamurtari Vlorë | ||||
| 1st(1st leg) | Turbina Cërrik | - | Egnatia Rrogozhine | 1:1 | ||
| 2nd (2nd leg) | Egnatia Rrogozhine | - | Turbina Cërrik | 1:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: Egnatia Rrogozhine | ||||
| 1st(1st leg) | KF Lushnja | - | FK Tomori Berat | 0:3 | ||
| 2nd (2nd leg) | FK Tomori Berat | - | KF Lushnja | 0:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 14/10/2021 12:30 | Winner: FK Tomori Berat | ||||
| 1st(1st leg) | Luzi United | - | KF Teuta Durrës | 1:4 | ||
| 2nd (2nd leg) | KF Teuta Durrës | - | Luzi United | 2:2 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: KF Teuta Durrës | ||||
| 1st(1st leg) | Labëria FC | - | FK Vllaznia | 2:1 | ||
| 2nd (2nd leg) | FK Vllaznia | - | Labëria FC | 4:0 | ||
| 1st(1st leg): 22/09/2021 15:00 | 2nd (2nd leg): 13/10/2021 12:30 | Winner: FK Vllaznia | ||||
