| 1 | Sat 7 Aug 2021 | 31-1 v Salford CitySalford City 1-1 Leyton Orient | Sky Bet League Two |
| 2 | Wed 11 Aug 2021 | 3 1-1 v Queens Park RangersLeyton Orient 1-1 Queens Park Rangers | Carabao Cup First Round |
| 3 | Sat 14 Aug 2021 | 33-0 v Exeter CityLeyton Orient 3-0 Exeter City | Sky Bet League Two |
| 4 | Tue 24 Aug 2021 | 30-2 v Harrogate TownLeyton Orient 0-2 Harrogate Town | Sky Bet League Two |
| 5 | Sat 28 Aug 2021 | 32-0 v Bradford CityLeyton Orient 2-0 Bradford City | Sky Bet League Two |
| 6 | Sat 4 Sep 2021 | 3 2-2 v Newport CountyNewport County 2-2 Leyton Orient | Sky Bet League Two |
| 7 | Sat 11 Sep 2021 | 34-0 v Oldham AthleticLeyton Orient 4-0 Oldham Athletic | Sky Bet League Two |
| 8 | Sat 18 Sep 2021 | 33-1 v Bristol RoversBristol Rovers 1-3 Leyton Orient | Sky Bet League Two |
| 9 | Sat 25 Sep 2021 | 30-0 v Mansfield TownLeyton Orient 0-0 Mansfield Town | Sky Bet League Two |
| 10 | Sat 2 Oct 2021 | 32-3 v Port ValePort Vale 3-2 Leyton Orient | Sky Bet League Two |
| 11 | Sat 9 Oct 2021 | 31-1 v BarrowBarrow 1-1 Leyton Orient | Sky Bet League Two |
| 12 | Sat 16 Oct 2021 | 30-0 v WalsallLeyton Orient 0-0 Walsall | Sky Bet League Two |
| 13 | Tue 19 Oct 2021 | 31-1 v Forest Green RoversLeyton Orient 1-1 Forest Green Rovers | Sky Bet League Two |
| 14 | Tue 9 Nov 2021 | 31-0 v Charlton AthleticLeyton Orient 1-0 Charlton Athletic | Papa John’s Trophy |
| 15 | Sat 27 Nov 2021 | 3 0-1 v Northampton TownNorthampton Town 1-0 Leyton Orient | Sky Bet League Two |
| 16 | Sat 11 Dec 2021 | 3 1-2 v Crawley TownLeyton Orient 1-2 Crawley Town | Sky Bet League Two |
| 17 | Sat 18 Dec 2021 | 30-1 v Tranmere RoversTranmere Rovers 1-0 Leyton Orient | Sky Bet League Two |
| 18 | Sun 9 Jan 2022 | 30-2 v Stoke CityStoke City 2-0 Leyton Orient | Emirates FA Cup Third Round |
| 19 | Sat 22 Jan 2022 | 3 0-0 v Port ValeLeyton Orient 0-0 Port Vale | Sky Bet League Two |
| 20 | Tue 25 Jan 2022 | 30-1 v Newport CountyLeyton Orient 0-1 Newport County | Sky Bet League Two |
| 21 | Sat 26 Feb 2022 | 30-1 v Carlisle UnitedLeyton Orient 0-1 Carlisle United | Sky Bet League Two |
| 22 | Tue 1 Mar 2022 | 32-2 v Colchester UnitedColchester United 2-2 Leyton Orient | Sky Bet League Two |
| 23 | Sat 5 Mar 2022 | 32-2 v StevenageLeyton Orient 2-2 Stevenage | Sky Bet League Two |
| 24 | Sat 12 Mar 2022 | 30-0 v Hartlepool UnitedHartlepool United 0-0 Leyton Orient | Sky Bet League Two |
| 25 | Tue 15 Mar 2022 | 3 1-1 v Forest Green RoversForest Green Rovers 1-1 Leyton Orient | Sky Bet League Two |
| 26 | Sat 19 Mar 2022 | 33-1 v RochdaleLeyton Orient 3-1 Rochdale | Sky Bet League Two |
| 27 | Tue 22 Mar 2022 | 33-0 v Harrogate TownHarrogate Town 0-3 Leyton Orient | Sky Bet League Two |
| 28 | Sat 26 Mar 2022 | 32-0 v BarrowLeyton Orient 2-0 Barrow | Sky Bet League Two |
| 29 | Tue 29 Mar 2022 | 30-2 v Oldham AthleticOldham Athletic 2-0 Leyton Orient | Sky Bet League Two |
| 30 | Sat 2 Apr 2022 | 32-0 v WalsallWalsall 0-2 Leyton Orient | Sky Bet League Two |
| 31 | Fri 15 Apr 2022 | 33-0 v Scunthorpe UnitedLeyton Orient 3-0 Scunthorpe United | Sky Bet League Two |
| 32 | Mon 18 Apr 2022 | 32-1 v Swindon TownSwindon Town 1-2 Leyton Orient | Sky Bet League Two |
| 33 | Sat 23 Apr 2022 | 32-4 v Northampton TownLeyton Orient 2-4 Northampton Town | Sky Bet League Two |
| 34 | Sat 30 Apr 2022 | 32-0 v Crawley TownCrawley Town 0-2 Leyton Orient | Sky Bet League Two |
| 35 | Sat 7 May 2022 | 30-1 v Tranmere RoversLeyton Orient 0-1 Tranmere Rovers | Sky Bet League Two |
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