| # | Team | MP | W | D | L | F | A | G | P |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Ajax | 9 | 7 | 1 | 1 | 32 | 2 | +30 | 22 |
| 2 | PSV Eindhoven | 9 | 7 | 0 | 2 | 22 | 12 | +10 | 21 |
| 3 | Utrecht | 9 | 5 | 2 | 2 | 19 | 10 | +9 | 17 |
| 4 | Willem II | 9 | 5 | 2 | 2 | 13 | 11 | +2 | 17 |
| 5 | Feyenoord | 8 | 5 | 1 | 2 | 22 | 11 | +11 | 16 |
| 6 | Vitesse | 9 | 5 | 1 | 3 | 9 | 15 | -6 | 16 |
| 7 | Twente | 9 | 4 | 3 | 2 | 15 | 11 | +4 | 15 |
| 8 | Heerenveen | 9 | 4 | 1 | 4 | 11 | 14 | -3 | 13 |
| 9 | AZ | 8 | 4 | 0 | 4 | 19 | 13 | +6 | 12 |
| 10 | Cambuur | 9 | 4 | 0 | 5 | 16 | 22 | -6 | 12 |
| 11 | NEC | 9 | 3 | 2 | 4 | 10 | 16 | -6 | 11 |
| 12 | Heracles Almelo | 8 | 3 | 1 | 4 | 11 | 14 | -3 | 10 |
| 13 | Go Ahead Eagles | 9 | 3 | 1 | 5 | 11 | 18 | -7 | 10 |
| 14 | Fortuna Sittard | 8 | 2 | 2 | 4 | 8 | 16 | -8 | 8 |
| 15 | RKC Waalwijk | 9 | 1 | 4 | 4 | 12 | 15 | -3 | 7 |
| 16 | Groningen | 9 | 1 | 4 | 4 | 8 | 15 | -7 | 7 |
| 17 | Sparta Rotterdam | 9 | 1 | 4 | 4 | 8 | 17 | -9 | 7 |
| 18 | PEC Zwolle | 9 | 0 | 1 | 8 | 3 | 17 | -14 | 1 |
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| Sunday, October 17, 2021 | ||
| Twente | 1 - 1 | Willem II |
| Sparta Rotterdam | 1 - 1 | Groningen |
| NEC | 0 - 1 | Vitesse |
| AZ | 5 - 1 | Utrecht |
| PSV Eindhoven | 3 - 1 | PEC Zwolle |
| Fortuna Sittard | 1 - 0 | Cambuur |
| Saturday, October 16, 2021 | ||
| Heerenveen | 0 - 2 | Ajax |
| Go Ahead Eagles | 4 - 2 | Heracles Almelo |
| Feyenoord | 2 - 2 | RKC Waalwijk |
| Sunday, October 3, 2021 | ||
| PSV Eindhoven | 2 - 1 | Sparta Rotterdam |
| Vitesse | 2 - 1 | Feyenoord |
| Cambuur | 1 - 3 | AZ |
| Ajax | 0 - 1 | Utrecht |
| Fortuna Sittard | 1 - 3 | NEC |
| Saturday, October 2, 2021 | ||
| PEC Zwolle | 0 - 1 | Heerenveen |
| Heracles Almelo | 3 - 2 | Willem II |
| RKC Waalwijk | 1 - 1 | Go Ahead Eagles |
| Friday, October 1, 2021 | ||
| Groningen | 1 - 1 | Twente |
| Friday, October 22, 2021 | ||
| Willem II | 23:30 | Fortuna Sittard |
| Saturday, October 23, 2021 | ||
| Utrecht | 22:15 | Heerenveen |
| PEC Zwolle | 23:30 | Heracles Almelo |
| Sunday, October 24, 2021 | ||
| RKC Waalwijk | 00:30 | Sparta Rotterdam |
| Twente | 15:45 | NEC |
| Cambuur | 18:00 | Feyenoord |
| Vitesse | 18:00 | Go Ahead Eagles |
| Ajax | 20:15 | PSV Eindhoven |
| Groningen | 23:30 | AZ |
| Saturday, October 30, 2021 | ||
| PSV Eindhoven | 20:00 | Twente |
| Heracles Almelo | 22:15 | Ajax |
| Heerenveen | 23:30 | Vitesse |
| Sunday, October 31, 2021 | ||
| AZ | 00:30 | PEC Zwolle |
| Sparta Rotterdam | 17:45 | Feyenoord |
| NEC | 20:00 | Groningen |
| Utrecht | 22:15 | Willem II |
| RKC Waalwijk | 22:15 | Cambuur |
| Monday, November 1, 2021 | ||
| Go Ahead Eagles | 01:30 | Fortuna Sittard |
| Saturday, November 6, 2021 | ||
| Twente | 01:30 | Heracles Almelo |
- Finish 1st: Champions League 3rd qualifying round on the Champions Path.
- Finish 2nd: Champions League 2nd qualifying round on the League Path.
- Finish 3rd/4th: Europa League 2nd qualifying round.
- 4th–7th/5th–8th 4th vs 7th and 5th vs 6th or 5th vs 8th and 6th vs 7th; the two winners play each other to qualify for:
Europa League 2nd qualifying round. - KNVB Cup winners play in the Europa League 3rd qualifying round