*Flamurtari Vlore 2-2 Apolonia Fier
| 13.10.2021 | Apolonia Fier | 1-1/p.5-6 | Flamurtari Vlore | |
| 22.09.2021 | Flamurtari Vlore | 1-1 | Apolonia Fier | |
Besa Kavaje 1-2 KS Pogradeci *
| 13.10.2021 | KS Pogradeci | 2-0 | Besa Kavaje | |
| 22.09.2021 | Besa Kavaje | 1-0 | KS Pogradeci | |
Erzeni Shijak 1-2 Dinamo Tirana *
| 14.10.2021 | Dinamo Tirana | 2-0 | Erzeni Shijak | |
| 22.09.2021 | Erzeni Shijak | 1-0 | Dinamo Tirana | |
Butrinti Sarandë 1-5 KF Laci *
| 13.10.2021 | KF Laci | 4-0 | Butrinti Sarandë | |
| 22.09.2021 | Butrinti Sarandë | 1-1 | KF Laci | |
KF Oriku 1-7 Bylis Ballsh *
| 14.10.2021 | Bylis Ballsh | 5-0 | KF Oriku | |
| 22.09.2021 | KF Oriku | 1-2 | Bylis Ballsh | |
KF Luzi 2008 3-6 KF Teuta Durres *
| 13.10.2021 | KF Teuta Durres | 2-2 | KF Luzi 2008 | |
| 22.09.2021 | KF Luzi 2008 | 1-4 | KF Teuta Durres | |
FK Vora 3-5 Korabi Peshkopi *
| 13.10.2021 | Korabi Peshkopi | 4-1 | FK Vora | |
| 22.09.2021 | FK Vora | 2-1 | Korabi Peshkopi | |
*Beselidhja Lezhe 4-2 KS Burreli
| 14.10.2021 | KS Burreli | 2-4 | Beselidhja Lezhe | |
| 22.09.2021 | Beselidhja Lezhe | 0-0 | KS Burreli | |
AF Elbasani 0-4 KS Kastrioti *
| 13.10.2021 | KS Kastrioti | 2-0 | AF Elbasani | |
| 22.09.2021 | AF Elbasani | 0-2 | KS Kastrioti | |
KS Lushnja 0-3 Tomori Berat *
| 14.10.2021 | Tomori Berat | 0-0 | KS Lushnja | |
| 22.09.2021 | KS Lushnja | 0-3 | Tomori Berat | |
Tërbuni Pukë 0-6 Partizani Tirana *
| 13.10.2021 | Partizani Tirana | 3-0 | Tërbuni Pukë | |
| 22.09.2021 | Tërbuni Pukë | 0-3 | Partizani Tirana | |
Veleciku Koplik 0-7 Skenderbeu *
| 13.10.2021 | Skenderbeu | 4-0 | Veleciku Koplik | |
| 22.09.2021 | Veleciku Koplik | 0-3 | Skenderbeu | |
Turbina Cërrik 1-2 Egnatia Rrogozhinë *
| 13.10.2021 | Egnatia Rrogozhinë | 1-0 | Turbina Cërrik | |
| 22.09.2021 | Turbina Cërrik | 1-1 | Egnatia Rrogozhinë | |
Labëria FC 2-5 Vllaznia Shkodër *
| 13.10.2021 | Vllaznia Shkodër | 4-0 | Labëria FC | |
| 22.09.2021 | Labëria FC | 2-1 | Vllaznia Shkodër | |