| 1 | Sat 7 Aug 2021 | 3 1-0 v Port ValeNorthampton Town 1-0 Port Vale | Sky Bet League Two |
| 2 | Sat 14 Aug 2021 | 31-0 v Colchester UnitedColchester United 0-1 Northampton Town | Sky Bet League Two |
| 3 | Sat 21 Aug 2021 | 31-3 v RochdaleNorthampton Town 1-3 Rochdale | Sky Bet League Two |
| 4 | Tue 24 Aug 2021 | 30-1 v AFC WimbledonNorthampton Town 0-1 AFC Wimbledon | Carabao Cup Second Round |
| 5 | Sat 28 Aug 2021 | 30-0 v Crawley TownCrawley Town 0-0 Northampton Town | Sky Bet League Two |
| 6 | Sat 4 Sep 2021 | 32-0 v Scunthorpe UnitedNorthampton Town 2-0 Scunthorpe United | Sky Bet League Two |
| 7 | Sat 11 Sep 2021 | 3 0-1 v Forest Green RoversForest Green Rovers 1-0 Northampton Town | Sky Bet League Two |
| 8 | Tue 14 Sep 2021 | 31-0 v Newport CountyNewport County 0-1 Northampton Town | Sky Bet League Two |
| 9 | Sat 18 Sep 2021 | 31-1 v Swindon TownNorthampton Town 1-1 Swindon Town | Sky Bet League Two |
| 10 | Sat 25 Sep 2021 | 32-2 v Salford CitySalford City 2-2 Northampton Town | Sky Bet League Two |
| 11 | Sat 2 Oct 2021 | 30-2 v Sutton UnitedNorthampton Town 0-2 Sutton United | Sky Bet League Two |
| 12 | Sat 9 Oct 2021 | 3 1-2 v Hartlepool UnitedHartlepool United 2-1 Northampton Town | Sky Bet League Two |
| 13 | Sat 16 Oct 2021 | 32-0 v Mansfield TownNorthampton Town 2-0 Mansfield Town | Sky Bet League Two |
| 14 | Tue 19 Oct 2021 | 33-0 v StevenageNorthampton Town 3-0 Stevenage | Sky Bet League Two |
| 15 | Sat 23 Oct 2021 | 32-0 v Tranmere RoversTranmere Rovers 0-2 Northampton Town | Sky Bet League Two |
| 16 | Sat 30 Oct 2021 | 33-0 v Carlisle UnitedNorthampton Town 3-0 Carlisle United | Sky Bet League Two |
| 17 | Tue 16 Nov 2021 | 3 1-3 v Cambridge UnitedCambridge United 3-1 Northampton Town | Emirates FA Cup First Round Replay |
| 18 | Sat 20 Nov 2021 | 31-1 v Bradford CityBradford City 1-1 Northampton Town | Sky Bet League Two |
| 19 | Tue 23 Nov 2021 | 32-1 v Oldham AthleticNorthampton Town 2-1 Oldham Athletic | Sky Bet League Two |
| 20 | Sat 27 Nov 2021 | 31-0 v Leyton OrientNorthampton Town 1-0 Leyton Orient | Sky Bet League Two |
| 21 | Tue 7 Dec 2021 | 32-1 v Exeter CityExeter City 1-2 Northampton Town | Sky Bet League Two |
| 22 | Sat 11 Dec 2021 | 3 2-1 v Harrogate TownHarrogate Town 1-2 Northampton Town | Sky Bet League Two |
| 23 | Sat 1 Jan 2022 | 32-5 v Swindon TownSwindon Town 5-2 Northampton Town | Sky Bet League Two |
| 24 | Sat 8 Jan 2022 | 30-1 v Crawley TownNorthampton Town 0-1 Crawley Town | Sky Bet League Two |
| 25 | Sat 15 Jan 2022 | 31-1 v Forest Green RoversNorthampton Town 1-1 Forest Green Rovers | Sky Bet League Two |
| 26 | Sat 22 Jan 2022 | 30-0 v Sutton UnitedSutton United 0-0 Northampton Town | Sky Bet League Two |
| 27 | Sat 29 Jan 2022 | 31-0 v Salford CityNorthampton Town 1-0 Salford City | Sky Bet League Two |
| 28 | Tue 1 Feb 2022 | 30-1 v BarrowNorthampton Town 0-1 Barrow | Sky Bet League Two |
| 29 | Sat 5 Feb 2022 | 31-0 v WalsallWalsall 0-1 Northampton Town | Sky Bet League Two |
| 30 | Sat 19 Feb 2022 | 33-0 v Colchester UnitedNorthampton Town 3-0 Colchester United | Sky Bet League Two |
| 31 | Tue 22 Feb 2022 | 30-0 v Scunthorpe UnitedScunthorpe United 0-0 Northampton Town | Sky Bet League Two |
| 32 | Sat 26 Feb 2022 | 30-1 v RochdaleRochdale 1-0 Northampton Town | Sky Bet League Two |
| 33 | Tue 1 Mar 2022 | 31-1 v WalsallNorthampton Town 1-1 Walsall | Sky Bet League Two |
| 34 | Sat 5 Mar 2022 | 33-2 v Tranmere RoversNorthampton Town 3-2 Tranmere Rovers | Sky Bet League Two |
| 35 | Sat 12 Mar 2022 | 31-2 v Carlisle UnitedCarlisle United 2-1 Northampton Town | Sky Bet League Two |
| 36 | Tue 15 Mar 2022 | 32-1 v StevenageStevenage 1-2 Northampton Town | Sky Bet League Two |
| 37 | Sat 19 Mar 2022 | 3 0-1 v Bristol RoversNorthampton Town 0-1 Bristol Rovers | Sky Bet League Two |
| 38 | Sat 26 Mar 2022 | 32-0 v Hartlepool UnitedNorthampton Town 2-0 Hartlepool United | Sky Bet League Two |
| 39 | Sat 2 Apr 2022 | 30-1 v Mansfield TownMansfield Town 1-0 Northampton Town | Sky Bet League Two |
| 40 | Sat 9 Apr 2022 | 30-0 v Bradford CityNorthampton Town 0-0 Bradford City | Sky Bet League Two |
| 41 | Fri 15 Apr 2022 | 32-0 v Oldham AthleticOldham Athletic 0-2 Northampton Town | Sky Bet League Two |
| 42 | Mon 18 Apr 2022 | 33-0 v Harrogate TownNorthampton Town 3-0 Harrogate Town | Sky Bet League Two |
| 43 | Sat 23 Apr 2022 | 34-2 v Leyton OrientLeyton Orient 2-4 Northampton Town | Sky Bet League Two |
| 44 | Sat 30 Apr 2022 | 31-1 v Exeter CityNorthampton Town 1-1 Exeter City | Sky Bet League Two |
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