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| 29/08/2021 | 15:00 | CS Onhaye | - | Eendracht Aalst | 1:0 (0:0, 0:0) aet | |
| 15:00 | RAA La Louviére | - | SC Dikkelvenne | 4:2 (3:0) | ||
| 15:00 | Royal Knokke FC | - | KRC Gent-Zeehaven | 3:2 (2:1, 2:2) aet | ||
| 15:00 | Belisia Bilzen | - | KFC Zwarte Leeuw | 1:0 (0:0) | ||
| 15:00 | KVK Tienen | - | RAS Jodoigne LS | 1:0 (0:0) | ||
| 15:00 | St. Eloois-Winkel Sport | - | Royal FC Mandel United | 5:4 (0:0, 0:0, 0:0) pso | ||
| 15:00 | Royal Francs Borains | - | Hoogstraten VV | 3:1 (2:0) | ||
| 04/09/2021 | 17:00 | FCV Dender EH | - | Waasland-Beveren | 1:0 (0:0) | |
| 18:30 | URSL Visé | - | RWDM Brussels FC | 0:1 (0:0) | ||
| 19:00 | Lierse Kempenzonen | - | Rupel Boom FC | 2:0 (0:0) | ||
| 05/09/2021 | 15:00 | RFC Liège | - | KVC Westerlo | 1:3 (1:2) | |
| 14/09/2021 | 18:30 | Lyra-Lierse Berlaar | - | SK Deinze | 0:5 (0:3) | |
| 19:00 | Royal Excel Mouscron | - | KVK Wellen | 3:1 (2:0) | ||
| 15/09/2021 | 19:00 | Diegem Sport | - | Lommel SK | 2:4 (1:2) | |
| 19:00 | KSC Lokeren-Temse | - | RFC Seraing | 0:3 (0:1) | ||
| 21/09/2021 | 19:30 | Union Saint-Gilloise | - | FC Lebbeke | 7:0 (1:0) |
