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| 24/09/2021 | 19:45 | Conwy Borough FC | - | The New Saints | 0:1 | |
| 19:45 | Caernarfon Town | - | Prestatyn Town | 3:0 | ||
| 19:45 | Colwyn Bay FC | - | Ruthin Town | 5:1 | ||
| 19:45 | Taff's Well AFC | - | Llantwit Major FC | 2:1 | ||
| 20:00 | Cambrian & Clydach | - | Penybont FC | 1:3 | ||
| 25/09/2021 | 12:45 | Trefelin BGC | - | Connah's Quay Nomads | 0:4 | |
| 14:30 | Aberystwyth Town | - | Cefn Druids | 4:1 | ||
| 14:30 | Buckley Town | - | Monmouth Town | 2:0 | ||
| 14:30 | Cardiff Metropolitan | - | Barry Town United | 3:0 | ||
| 14:30 | Saltney Town | - | Penrhyncoch FC | 4:2 pso | ||
| 14:30 | Swansea University | - | Bangor City | 1:0 | ||
| 14:30 | Penrhiwceiber Rangers | - | Flint Town United | 1:3 | ||
| 14:30 | Airbus UK | - | Haverfordwest County | 1:2 | ||
| 14:30 | Bala Town | - | Pontypridd Town | 5:0 | ||
| 14:30 | Newtown AFC | - | Carmarthen Town | 4:6 pso | ||
| 14:30 | Dinas Powys | - | Guilsfield FC | 2:4 |
