| 1 | Sat 7 Aug 2021 | 2 1-1 v Cheltenham TownCrewe Alexandra 1-1 Cheltenham Town | Sky Bet League One |
| 2 | Sat 14 Aug 2021 | 20-2 v PortsmouthPortsmouth 2-0 Crewe Alexandra | Sky Bet League One |
| 3 | Tue 17 Aug 2021 | 20-1 v Oxford UnitedOxford United 1-0 Crewe Alexandra | Sky Bet League One |
| 4 | Sat 21 Aug 2021 | 2 0-1 v Accrington StanleyCrewe Alexandra 0-1 Accrington Stanley | Sky Bet League One |
| 5 | Tue 24 Aug 2021 | 20-3 v Leeds UnitedLeeds United 3-0 Crewe Alexandra | Carabao Cup Second Round |
| 6 | Sat 28 Aug 2021 | 20-2 v Charlton AthleticCharlton Athletic 2-0 Crewe Alexandra | Sky Bet League One |
| 7 | Tue 31 Aug 2021 | 21-0 v Shrewsbury TownShrewsbury Town 0-1 Crewe Alexandra | Papa John’s Trophy |
| 8 | Sat 11 Sep 2021 | 2 1-1 v Shrewsbury TownShrewsbury Town 1-1 Crewe Alexandra | Sky Bet League One |
| 9 | Sat 18 Sep 2021 | 22-0 v Burton AlbionCrewe Alexandra 2-0 Burton Albion | Sky Bet League One |
| 10 | Tue 21 Sep 2021 | 21-3 v MorecambeCrewe Alexandra 1-3 Morecambe | Sky Bet League One |
| 11 | Sat 25 Sep 2021 | 21-1 v Rotherham UnitedRotherham United 1-1 Crewe Alexandra | Sky Bet League One |
| 12 | Tue 28 Sep 2021 | 21-1 v Plymouth ArgylePlymouth Argyle 1-1 Crewe Alexandra | Sky Bet League One |
| 13 | Sat 2 Oct 2021 | 2 2-2 v Cambridge UnitedCrewe Alexandra 2-2 Cambridge United | Sky Bet League One |
| 14 | Tue 19 Oct 2021 | 20-4 v SunderlandCrewe Alexandra 0-4 Sunderland | Sky Bet League One |
| 15 | Sat 11 Dec 2021 | 20-2 v Sheffield WednesdayCrewe Alexandra 0-2 Sheffield Wednesday | Sky Bet League One |
| 16 | Wed 29 Dec 2021 | 22-1 v MorecambeMorecambe 1-2 Crewe Alexandra | Sky Bet League One |
| 17 | Sat 1 Jan 2022 | 21-4 v Burton AlbionBurton Albion 4-1 Crewe Alexandra | Sky Bet League One |
| 18 | Tue 4 Jan 2022 | 2 2-4 v Rotherham UnitedCrewe Alexandra 2-4 Rotherham United | Papa John’s Trophy Third Round |
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