| October 3, 2021 | ||
| PSV Eindhoven | 2 - 1 | Sparta Rotterdam |
| Vitesse | 2 - 1 | Feyenoord |
| Cambuur | 1 - 3 | AZ |
| Ajax | 0 - 1 | Utrecht |
| October 2, 2021 | ||
| Fortuna Sittard | 1 - 3 | NEC |
| PEC Zwolle | 0 - 1 | Heerenveen |
| Heracles Almelo | 3 - 2 | Willem II |
| RKC Waalwijk | 1 - 1 | Go Ahead Eagles |
| October 1, 2021 | ||
| Groningen | 1 - 1 | Twente |
| September 26, 2021 | ||
| Heracles Almelo | 1 - 0 | RKC Waalwijk |
| Heerenveen | 2 - 3 | Twente |
| AZ | 5 - 0 | Go Ahead Eagles |
| Sparta Rotterdam | 0 - 4 | Cambuur |
| September 25, 2021 | ||
| Feyenoord | 5 - 3 | NEC |
| Utrecht | 5 - 1 | PEC Zwolle |
| Ajax | 3 - 0 | Groningen |
| Vitesse | 1 - 1 | Fortuna Sittard |
| Willem II | 2 - 1 | PSV Eindhoven |
| September 23, 2021 | ||
| Twente | 3 - 1 | AZ |
| Cambuur | 2 - 1 | Heracles Almelo |
