| 1. Round | 22/08/2021 | Benevento Calcio | - | US Alessandria 1912 | 4:3 | ||||
| 2. Round | 27/08/2021 | Pisa SC | - | US Alessandria 1912 | 2:0 | ||||
| 5. Round | 21/09/2021 | US Alessandria 1912 | - | Ascoli Calcio | 1:3 | ||||
| 9. Round | 22/10/2021 | US Alessandria 1912 | - | FC Crotone | 1:0 | ||||
| 10. Round | 28/10/2021 | US Alessandria 1912 | - | Frosinone Calcio | 1:1 | ||||
| 11. Round | 01/11/2021 | AC Monza | - | US Alessandria 1912 | 1:0 | ||||
| 12. Round | 06/11/2021 | US Alessandria 1912 | - | Ternana Calcio | 0:2 | ||||
| 13. Round | 20/11/2021 | SPAL 2013 Ferrara | - | US Alessandria 1912 | 2:3 |  |
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| 14. Round | 27/11/2021 | US Alessandria 1912 | - | US Cremonese | 1:0 |  |
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| 15. Round | 30/11/2021 | Pordenone Calcio | - | US Alessandria 1912 | 2:0 | ||||
| 16. Round | 05/12/2021 | US Alessandria 1912 | - | AS Cittadella | 0:1 | ||||
| 17. Round | 12/12/2021 | Reggina 1914 | - | US Alessandria 1912 | 0:4 | ||||
| 18. Round | 19/12/2021 | US Alessandria 1912 | - | Parma Calcio 1913 | 0:2 |
Italy