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| 21.09.2021 | 20:45 | Bangor City | - | Bala Town | 7:8 (0:0, 0:0) i.E. | |
| 20:45 | Newtown AFC | - | Caernarfon Town | 5:0 (2:0) | ||
| 20:45 | Prestatyn Town | - | Holywell Town | 3:4 (2:1) | ||
| 20:45 | Connah's Quay Nomads | - | Airbus UK | 6:3 (3:3) | ||
| 20:45 | Haverfordwest County | - | Undy Athletic | 5:0 (2:0) | ||
| 20:45 | Barry Town United | - | Trefelin BGC | 3:0 (0:0) | ||
| 21:00 | Aberystwyth Town | - | Cardiff Metropolitan | 2:5 (0:3) | ||
| 22.09.2021 | 20:45 | Penrhyncoch FC | - | Pontypridd Town | 1:3 (1:2) |
