| 1 | Sat 31 Jul 2021 | 20-5 v AFC BournemouthAFC Bournemouth 5-0 Milton Keynes Dons | Carabao Cup First Round |
| 2 | Sat 7 Aug 2021 | 23-3 v Bolton WanderersBolton Wanderers 3-3 Milton Keynes Dons | Sky Bet League One |
| 3 | Sat 14 Aug 2021 | 21-2 v SunderlandMilton Keynes Dons 1-2 Sunderland | Sky Bet League One |
| 4 | Tue 17 Aug 2021 | 22-1 v Charlton AthleticMilton Keynes Dons 2-1 Charlton Athletic | Sky Bet League One |
| 5 | Sat 21 Aug 2021 | 22-2 v Ipswich TownIpswich Town 2-2 Milton Keynes Dons | Sky Bet League One |
| 6 | Sat 28 Aug 2021 | 22-0 v Accrington StanleyMilton Keynes Dons 2-0 Accrington Stanley | Sky Bet League One |
| 7 | Tue 31 Aug 2021 | 22-1 v Burton AlbionBurton Albion 1-2 Milton Keynes Dons | Papa John’s Trophy |
| 8 | Sat 4 Sep 2021 | 21-1 v Cheltenham TownCheltenham Town 1-1 Milton Keynes Dons | Sky Bet League One |
| 9 | Sat 11 Sep 2021 | 21-0 v PortsmouthMilton Keynes Dons 1-0 Portsmouth | Sky Bet League One |
| 10 | Sat 18 Sep 2021 | 24-1 v GillinghamGillingham 1-4 Milton Keynes Dons | Sky Bet League One |
| 11 | Sat 25 Sep 2021 | 21-0 v Wycombe WanderersMilton Keynes Dons 1-0 Wycombe Wanderers | Sky Bet League One |
| 12 | Tue 5 Oct 2021 | 22-1 v Wycombe WanderersMilton Keynes Dons 2-1 Wycombe Wanderers | Papa John’s Trophy |
| 13 | Sat 16 Oct 2021 | 20-1 v Shrewsbury TownShrewsbury Town 1-0 Milton Keynes Dons | Sky Bet League One |
| 14 | Sat 23 Oct 2021 | 20-3 v Rotherham UnitedMilton Keynes Dons 0-3 Rotherham United | Sky Bet League One |
| 15 | Sat 13 Nov 2021 | 24-1 v Cambridge UnitedMilton Keynes Dons 4-1 Cambridge United | Sky Bet League One |
| 16 | Tue 16 Nov 2021 | 21-2 v StevenageStevenage 2-1 Milton Keynes Dons | Emirates FA Cup First Round Replay |
| 17 | Wed 8 Dec 2021 | 21-1 v Plymouth ArgyleMilton Keynes Dons 1-1 Plymouth Argyle | Sky Bet League One |
| 18 | Sat 11 Dec 2021 | 21-2 v Oxford UnitedMilton Keynes Dons 1-2 Oxford United | Sky Bet League One |
| 19 | Tue 4 Jan 2022 | 20-1 v Charlton AthleticCharlton Athletic 1-0 Milton Keynes Dons | Papa John’s Trophy Third Round |
| 20 | Sat 8 Jan 2022 | 21-1 v Accrington StanleyAccrington Stanley 1-1 Milton Keynes Dons | Sky Bet League One |
| 21 | Tue 11 Jan 2022 | 21-0 v AFC WimbledonMilton Keynes Dons 1-0 AFC Wimbledon | Sky Bet League One |
| 22 | Sat 15 Jan 2022 | 22-1 v PortsmouthPortsmouth 1-2 Milton Keynes Dons | Sky Bet League One |
| 23 | Sat 22 Jan 2022 | 20-1 v Doncaster RoversMilton Keynes Dons 0-1 Doncaster Rovers | Sky Bet League One |
| 24 | Tue 25 Jan 2022 | 21-0 v Burton AlbionBurton Albion 0-1 Milton Keynes Dons | Sky Bet League One |
| 25 | Sat 29 Jan 2022 | 21-0 v Wycombe WanderersWycombe Wanderers 0-1 Milton Keynes Dons | Sky Bet League One |
| 26 | Sat 5 Feb 2022 | 22-1 v Lincoln CityMilton Keynes Dons 2-1 Lincoln City | Sky Bet League One |
| 27 | Sat 12 Feb 2022 | 2 0-0 v Ipswich TownMilton Keynes Dons 0-0 Ipswich Town | Sky Bet League One |
| 28 | Sat 19 Feb 2022 | 22-1 v SunderlandSunderland 1-2 Milton Keynes Dons | Sky Bet League One |
| 29 | Tue 22 Feb 2022 | 22-0 v Charlton AthleticCharlton Athletic 0-2 Milton Keynes Dons | Sky Bet League One |
| 30 | Sat 26 Feb 2022 | 22-0 v Bolton WanderersMilton Keynes Dons 2-0 Bolton Wanderers | Sky Bet League One |
| 31 | Sat 5 Mar 2022 | 22-1 v Rotherham UnitedRotherham United 1-2 Milton Keynes Dons | Sky Bet League One |
| 32 | Tue 8 Mar 2022 | 23-1 v Cheltenham TownMilton Keynes Dons 3-1 Cheltenham Town | Sky Bet League One |
| 33 | Sun 8 May 2022 | 21-0 v Wycombe WanderersMilton Keynes Dons 1-0 Wycombe Wanderers | Sky Bet League One Play-off Semi Final |
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