| Date | Home | Away | Result |
|---|---|---|---|
| 9/17/21 1:45 PM | KSV Cercle Brügge | KAS Eupen | 1-2 |
| 9/18/21 9:15 AM | KV Oostende | K. Beerschot V.A. | 3-1 |
| 9/18/21 11:30 AM | Royale Union Saint-Gilloise | SV Zulte-Waregem | 2-1 |
| 9/18/21 11:30 AM | KV Mechelen | OH Leuven | 2-0 |
| 9/18/21 1:45 PM | Sporting Charleroi | Club Brugge | 0-1 |
| 9/19/21 6:30 AM | Sint-Truidense VV | KRC Genk | 1-2 |
| 9/19/21 9:00 AM | Royal Antwerp FC | RFC Seraing | 2-1 |
| 9/19/21 11:30 AM | Standard Liège | RSC Anderlecht | 0-1 |
| 9/19/21 2:00 PM | KV Kortrijk | KAA Gent | 1-0 |