| 1 | Sat 7 Aug 2021 | 31-1 v Cheltenham TownCrewe Alexandra 1-1 Cheltenham Town | Sky Bet League One |
| 2 | Sat 14 Aug 2021 | 30-2 v PortsmouthPortsmouth 2-0 Crewe Alexandra | Sky Bet League One |
| 3 | Tue 17 Aug 2021 | 30-1 v Oxford UnitedOxford United 1-0 Crewe Alexandra | Sky Bet League One |
| 4 | Sat 21 Aug 2021 | 30-1 v Accrington StanleyCrewe Alexandra 0-1 Accrington Stanley | Sky Bet League One |
| 5 | Tue 24 Aug 2021 | 3 0-3 v Leeds UnitedLeeds United 3-0 Crewe Alexandra | Carabao Cup Second Round |
| 6 | Sat 28 Aug 2021 | 3 0-2 v Charlton AthleticCharlton Athletic 2-0 Crewe Alexandra | Sky Bet League One |
| 7 | Sat 11 Sep 2021 | 3 1-1 v Shrewsbury TownShrewsbury Town 1-1 Crewe Alexandra | Sky Bet League One |
| 8 | Sat 18 Sep 2021 | 32-0 v Burton AlbionCrewe Alexandra 2-0 Burton Albion | Sky Bet League One |
| 9 | Tue 21 Sep 2021 | 31-3 v MorecambeCrewe Alexandra 1-3 Morecambe | Sky Bet League One |
| 10 | Sat 25 Sep 2021 | 31-1 v Rotherham UnitedRotherham United 1-1 Crewe Alexandra | Sky Bet League One |
| 11 | Tue 28 Sep 2021 | 31-1 v Plymouth ArgylePlymouth Argyle 1-1 Crewe Alexandra | Sky Bet League One |
| 12 | Sat 2 Oct 2021 | 32-2 v Cambridge UnitedCrewe Alexandra 2-2 Cambridge United | Sky Bet League One |
| 13 | Sat 16 Oct 2021 | 30-3 v Fleetwood TownFleetwood Town 3-0 Crewe Alexandra | Sky Bet League One |
| 14 | Sat 23 Oct 2021 | 3 1-2 v Wycombe WanderersWycombe Wanderers 2-1 Crewe Alexandra | Sky Bet League One |
| 15 | Sat 30 Oct 2021 | 31-4 v Milton Keynes DonsCrewe Alexandra 1-4 Milton Keynes Dons | Sky Bet League One |
| 16 | Tue 2 Nov 2021 | 31-1 v Doncaster RoversCrewe Alexandra 1-1 Doncaster Rovers | Sky Bet League One |
| 17 | Sat 6 Nov 2021 | 30-3 v Swindon TownCrewe Alexandra 0-3 Swindon Town | Emirates FA Cup First Round |
| 18 | Fri 12 Nov 2021 | 30-2 v Bolton WanderersBolton Wanderers 2-0 Crewe Alexandra | Sky Bet League One |
| 19 | Sat 20 Nov 2021 | 32-0 v GillinghamCrewe Alexandra 2-0 Gillingham | Sky Bet League One |
| 20 | Tue 23 Nov 2021 | 32-3 v AFC WimbledonAFC Wimbledon 3-2 Crewe Alexandra | Sky Bet League One |
| 21 | Sun 28 Nov 2021 | 31-2 v Ipswich TownIpswich Town 2-1 Crewe Alexandra | Sky Bet League One |
| 22 | Tue 7 Dec 2021 | 32-0 v Lincoln CityCrewe Alexandra 2-0 Lincoln City | Sky Bet League One |
| 23 | Sat 11 Dec 2021 | 30-2 v Sheffield WednesdayCrewe Alexandra 0-2 Sheffield Wednesday | Sky Bet League One |
| 24 | Wed 29 Dec 2021 | 3 2-1 v MorecambeMorecambe 1-2 Crewe Alexandra | Sky Bet League One |
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