| Date | Home | Away | Result |
|---|---|---|---|
| 9/10/21 1:45 PM | Club Brugge | KV Oostende | 3-0 |
| 9/11/21 9:15 AM | KAS Eupen | Royal Antwerp FC | 0-1 |
| 9/11/21 11:30 AM | SV Zulte-Waregem | KSV Cercle Brügge | 2-4 |
| 9/12/21 6:30 AM | RSC Anderlecht | KV Mechelen | 7-2 |
| 9/12/21 9:00 AM | KAA Gent | Sporting Charleroi | 2-3 |
| 9/12/21 11:30 AM | RFC Seraing | Standard Liège | 0-1 |
| 9/12/21 2:00 PM | KRC Genk | Royale Union Saint-Gilloise | 1-1 |
| 9/12/21 2:00 PM | OH Leuven | KV Kortrijk | 2-1 |
| 9/13/21 1:00 PM | K. Beerschot V.A. | Sint-Truidense VV | 0-1 |