| August 13, 2021 | ||
| Go Ahead Eagles | 20:00 | Heerenveen |
| August 14, 2021 | ||
| RKC Waalwijk | 16:30 | AZ |
| Heracles Almelo | 18:45 | PSV Eindhoven |
| Fortuna Sittard | 20:00 | Twente |
| Ajax | 21:00 | NEC |
| August 15, 2021 | ||
| Cambuur | 12:15 | Groningen |
| PEC Zwolle | 14:30 | Vitesse |
| Utrecht | 14:30 | Sparta Rotterdam |
| Willem II | 16:45 | Feyenoord |
| August 20, 2021 | ||
| NEC | 20:00 | PEC Zwolle |
| August 21, 2021 | ||
| Heerenveen | 18:45 | RKC Waalwijk |
| PSV Eindhoven | 20:00 | Cambuur |
| Sparta Rotterdam | 20:00 | Heracles Almelo |
| Groningen | 21:00 | Utrecht |
| August 22, 2021 | ||
| Twente | 12:15 | Ajax |
| Feyenoord | 14:30 | Go Ahead Eagles |
| Vitesse | 14:30 | Willem II |
| August 27, 2021 | ||
| Fortuna Sittard | 20:00 | RKC Waalwijk |
