| 1 | Sat 7 Aug 2021 | 40-0 v Carlisle UnitedCarlisle United 0-0 Colchester United | Sky Bet League Two |
| 2 | Sat 14 Aug 2021 | 40-1 v Northampton TownColchester United 0-1 Northampton Town | Sky Bet League Two |
| 3 | Tue 17 Aug 2021 | 41-1 v Mansfield TownColchester United 1-1 Mansfield Town | Sky Bet League Two |
| 4 | Sat 21 Aug 2021 | 42-1 v Oldham AthleticOldham Athletic 1-2 Colchester United | Sky Bet League Two |
| 5 | Fri 27 Aug 2021 | 41-1 v RochdaleRochdale 1-1 Colchester United | Sky Bet League Two |
| 6 | Fri 10 Sep 2021 | 4 3-2 v BarrowBarrow 2-3 Colchester United | Sky Bet League Two |
| 7 | Sat 25 Sep 2021 | 40-0 v Swindon TownSwindon Town 0-0 Colchester United | Sky Bet League Two |
| 8 | Sat 2 Oct 2021 | 40-2 v Salford CityColchester United 0-2 Salford City | Sky Bet League Two |
| 9 | Fri 8 Oct 2021 | 40-2 v Tranmere RoversTranmere Rovers 2-0 Colchester United | Sky Bet League Two |
| 10 | Sat 16 Oct 2021 | 4 1-0 v Harrogate TownColchester United 1-0 Harrogate Town | Sky Bet League Two |
| 11 | Tue 19 Oct 2021 | 4 1-1 v Bristol RoversColchester United 1-1 Bristol Rovers | Sky Bet League Two |
| 12 | Sat 23 Oct 2021 | 4 0-3 v Port ValePort Vale 3-0 Colchester United | Sky Bet League Two |
| 13 | Tue 26 Oct 2021 | 41-3 v Sutton UnitedColchester United 1-3 Sutton United | Sky Bet League Two |
| 14 | Sat 30 Oct 2021 | 4 2-1 v Scunthorpe UnitedColchester United 2-1 Scunthorpe United | Sky Bet League Two |
| 15 | Tue 9 Nov 2021 | 40-0 v Ipswich TownIpswich Town 0-0 Colchester United | Papa John’s Trophy |
| 16 | Sat 20 Nov 2021 | 40-1 v StevenageStevenage 1-0 Colchester United | Sky Bet League Two |
| 17 | Tue 23 Nov 2021 | 43-1 v Exeter CityColchester United 3-1 Exeter City | Sky Bet League Two |
| 18 | Fri 26 Nov 2021 | 41-1 v Newport CountyColchester United 1-1 Newport County | Sky Bet League Two |
| 19 | Sun 5 Dec 2021 | 41-2 v Wigan AthleticColchester United 1-2 Wigan Athletic | Emirates FA Cup Second Round |
| 20 | Wed 8 Dec 2021 | 40-0 v Bradford CityBradford City 0-0 Colchester United | Sky Bet League Two |
| 21 | Sat 11 Dec 2021 | 40-3 v WalsallWalsall 3-0 Colchester United | Sky Bet League Two |
| 22 | Sat 1 Jan 2022 | 41-3 v Crawley TownCrawley Town 3-1 Colchester United | Sky Bet League Two |
| 23 | Tue 4 Jan 2022 | 41-2 v Sutton UnitedSutton United 2-1 Colchester United | Papa John’s Trophy Third Round |
| 24 | Tue 11 Jan 2022 | 40-2 v Forest Green RoversForest Green Rovers 2-0 Colchester United | Sky Bet League Two |
| 25 | Sat 15 Jan 2022 | 40-2 v BarrowColchester United 0-2 Barrow | Sky Bet League Two |
| 26 | Tue 18 Jan 2022 | 42-3 v Sutton UnitedSutton United 3-2 Colchester United | Sky Bet League Two |
| 27 | Sat 22 Jan 2022 | 43-0 v Salford CitySalford City 0-3 Colchester United | Sky Bet League Two |
| 28 | Sat 29 Jan 2022 | 4 1-1 v Swindon TownColchester United 1-1 Swindon Town | Sky Bet League Two |
| 29 | Tue 8 Feb 2022 | 41-2 v Mansfield TownMansfield Town 2-1 Colchester United | Sky Bet League Two |
| 30 | Sat 12 Feb 2022 | 4 2-2 v Carlisle UnitedColchester United 2-2 Carlisle United | Sky Bet League Two |
| 31 | Sat 19 Feb 2022 | 40-3 v Northampton TownNorthampton Town 3-0 Colchester United | Sky Bet League Two |
| 32 | Tue 22 Feb 2022 | 41-2 v Hartlepool UnitedColchester United 1-2 Hartlepool United | Sky Bet League Two |
| 33 | Sat 26 Feb 2022 | 41-1 v Oldham AthleticColchester United 1-1 Oldham Athletic | Sky Bet League Two |
| 34 | Tue 1 Mar 2022 | 42-2 v Leyton OrientColchester United 2-2 Leyton Orient | Sky Bet League Two |
| 35 | Sat 5 Mar 2022 | 41-0 v Port ValeColchester United 1-0 Port Vale | Sky Bet League Two |
| 36 | Sat 12 Mar 2022 | 43-1 v Scunthorpe UnitedScunthorpe United 1-3 Colchester United | Sky Bet League Two |
| 37 | Tue 15 Mar 2022 | 40-1 v Bristol RoversBristol Rovers 1-0 Colchester United | Sky Bet League Two |
| 38 | Mon 21 Mar 2022 | 40-1 v Forest Green RoversColchester United 0-1 Forest Green Rovers | Sky Bet League Two |
| 39 | Sat 26 Mar 2022 | 41-0 v Tranmere RoversColchester United 1-0 Tranmere Rovers | Sky Bet League Two |
| 40 | Sat 2 Apr 2022 | 42-1 v Harrogate TownHarrogate Town 1-2 Colchester United | Sky Bet League Two |
| 41 | Sat 9 Apr 2022 | 40-2 v StevenageColchester United 0-2 Stevenage | Sky Bet League Two |
| 42 | Fri 15 Apr 2022 | 40-2 v Exeter CityExeter City 2-0 Colchester United | Sky Bet League Two |
| 43 | Mon 18 Apr 2022 | 43-0 v Bradford CityColchester United 3-0 Bradford City | Sky Bet League Two |
| 44 | Fri 22 Apr 2022 | 42-1 v Newport CountyNewport County 1-2 Colchester United | Sky Bet League Two |
| 45 | Sat 30 Apr 2022 | 42-2 v WalsallColchester United 2-2 Walsall | Sky Bet League Two |
| 46 | Sat 7 May 2022 | 42-0 v Hartlepool UnitedHartlepool United 0-2 Colchester United | Sky Bet League Two |
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