| 1 | Tue 17 Aug 2021 | 3 2-1 v Charlton AthleticMilton Keynes Dons 2-1 Charlton Athletic | Sky Bet League One |
| 2 | Sat 21 Aug 2021 | 32-2 v Ipswich TownIpswich Town 2-2 Milton Keynes Dons | Sky Bet League One |
| 3 | Sat 28 Aug 2021 | 3 2-0 v Accrington StanleyMilton Keynes Dons 2-0 Accrington Stanley | Sky Bet League One |
| 4 | Sat 4 Sep 2021 | 31-1 v Cheltenham TownCheltenham Town 1-1 Milton Keynes Dons | Sky Bet League One |
| 5 | Sat 11 Sep 2021 | 31-0 v PortsmouthMilton Keynes Dons 1-0 Portsmouth | Sky Bet League One |
| 6 | Sat 18 Sep 2021 | 34-1 v GillinghamGillingham 1-4 Milton Keynes Dons | Sky Bet League One |
| 7 | Sat 25 Sep 2021 | 31-0 v Wycombe WanderersMilton Keynes Dons 1-0 Wycombe Wanderers | Sky Bet League One |
| 8 | Tue 28 Sep 2021 | 33-3 v Fleetwood TownMilton Keynes Dons 3-3 Fleetwood Town | Sky Bet League One |
| 9 | Sat 2 Oct 2021 | 31-2 v Doncaster RoversDoncaster Rovers 2-1 Milton Keynes Dons | Sky Bet League One |
| 10 | Sat 16 Oct 2021 | 30-1 v Shrewsbury TownShrewsbury Town 1-0 Milton Keynes Dons | Sky Bet League One |
| 11 | Tue 19 Oct 2021 | 32-1 v Wigan AthleticWigan Athletic 1-2 Milton Keynes Dons | Sky Bet League One |
| 12 | Sat 23 Oct 2021 | 30-3 v Rotherham UnitedMilton Keynes Dons 0-3 Rotherham United | Sky Bet League One |
| 13 | Sat 30 Oct 2021 | 34-1 v Crewe AlexandraCrewe Alexandra 1-4 Milton Keynes Dons | Sky Bet League One |
| 14 | Sat 6 Nov 2021 | 32-2 v StevenageMilton Keynes Dons 2-2 Stevenage | Emirates FA Cup First Round |
| 15 | Sat 13 Nov 2021 | 34-1 v Cambridge UnitedMilton Keynes Dons 4-1 Cambridge United | Sky Bet League One |
| 16 | Sat 20 Nov 2021 | 31-0 v Burton AlbionMilton Keynes Dons 1-0 Burton Albion | Sky Bet League One |
| 17 | Tue 23 Nov 2021 | 31-2 v Sheffield WednesdaySheffield Wednesday 2-1 Milton Keynes Dons | Sky Bet League One |
| 18 | Sat 27 Nov 2021 | 34-0 v MorecambeMorecambe 0-4 Milton Keynes Dons | Sky Bet League One |
| 19 | Wed 8 Dec 2021 | 31-1 v Plymouth ArgyleMilton Keynes Dons 1-1 Plymouth Argyle | Sky Bet League One |
| 20 | Sat 11 Dec 2021 | 31-2 v Oxford UnitedMilton Keynes Dons 1-2 Oxford United | Sky Bet League One |
| 21 | Sun 26 Dec 2021 | 33-2 v Lincoln CityLincoln City 2-3 Milton Keynes Dons | Sky Bet League One |
| 22 | Sat 1 Jan 2022 | 30-0 v GillinghamMilton Keynes Dons 0-0 Gillingham | Sky Bet League One |
| 23 | Sat 8 Jan 2022 | 3 1-1 v Accrington StanleyAccrington Stanley 1-1 Milton Keynes Dons | Sky Bet League One |
| 24 | Tue 11 Jan 2022 | 31-0 v AFC WimbledonMilton Keynes Dons 1-0 AFC Wimbledon | Sky Bet League One |
| 25 | Sat 15 Jan 2022 | 32-1 v PortsmouthPortsmouth 1-2 Milton Keynes Dons | Sky Bet League One |
| 26 | Sat 22 Jan 2022 | 30-1 v Doncaster RoversMilton Keynes Dons 0-1 Doncaster Rovers | Sky Bet League One |
| 27 | Tue 25 Jan 2022 | 31-0 v Burton AlbionBurton Albion 0-1 Milton Keynes Dons | Sky Bet League One |
| 28 | Sat 29 Jan 2022 | 31-0 v Wycombe WanderersWycombe Wanderers 0-1 Milton Keynes Dons | Sky Bet League One |
| 29 | Sat 5 Feb 2022 | 32-1 v Lincoln CityMilton Keynes Dons 2-1 Lincoln City | Sky Bet League One |
| 30 | Tue 8 Feb 2022 | 3 1-1 v Fleetwood TownFleetwood Town 1-1 Milton Keynes Dons | Sky Bet League One |
| 31 | Sat 12 Feb 2022 | 3 0-0 v Ipswich TownMilton Keynes Dons 0-0 Ipswich Town | Sky Bet League One |
| 32 | Sat 19 Feb 2022 | 32-1 v SunderlandSunderland 1-2 Milton Keynes Dons | Sky Bet League One |
| 33 | Tue 22 Feb 2022 | 32-0 v Charlton AthleticCharlton Athletic 0-2 Milton Keynes Dons | Sky Bet League One |
| 34 | Sat 26 Feb 2022 | 32-0 v Bolton WanderersMilton Keynes Dons 2-0 Bolton Wanderers | Sky Bet League One |
| 35 | Sat 5 Mar 2022 | 3 2-1 v Rotherham UnitedRotherham United 1-2 Milton Keynes Dons | Sky Bet League One |
| 36 | Tue 8 Mar 2022 | 33-1 v Cheltenham TownMilton Keynes Dons 3-1 Cheltenham Town | Sky Bet League One |
| 37 | Sat 12 Mar 2022 | 31-1 v Wigan AthleticMilton Keynes Dons 1-1 Wigan Athletic | Sky Bet League One |
| 38 | Sat 19 Mar 2022 | 31-0 v Cambridge UnitedCambridge United 0-1 Milton Keynes Dons | Sky Bet League One |
| 39 | Sat 2 Apr 2022 | 32-0 v Shrewsbury TownMilton Keynes Dons 2-0 Shrewsbury Town | Sky Bet League One |
| 40 | Tue 5 Apr 2022 | 32-1 v Crewe AlexandraMilton Keynes Dons 2-1 Crewe Alexandra | Sky Bet League One |
| 41 | Sat 9 Apr 2022 | 31-1 v AFC WimbledonAFC Wimbledon 1-1 Milton Keynes Dons | Sky Bet League One |
| 42 | Sat 16 Apr 2022 | 32-3 v Sheffield WednesdayMilton Keynes Dons 2-3 Sheffield Wednesday | Sky Bet League One |
| 43 | Tue 19 Apr 2022 | 30-1 v Oxford UnitedOxford United 1-0 Milton Keynes Dons | Sky Bet League One |
| 44 | Sat 23 Apr 2022 | 3 2-0 v MorecambeMilton Keynes Dons 2-0 Morecambe | Sky Bet League One |
| 45 | Sat 30 Apr 2022 | 35-0 v Plymouth ArgylePlymouth Argyle 0-5 Milton Keynes Dons | Sky Bet League One |
| 46 | Thu 5 May 2022 | 30-2 v Wycombe WanderersWycombe Wanderers 2-0 Milton Keynes Dons | Sky Bet League One Play-off Semi Final |
| 47 | Sun 8 May 2022 | 31-0 v Wycombe WanderersMilton Keynes Dons 1-0 Wycombe Wanderers | Sky Bet League One Play-off Semi Final |
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