| 1 | Sat 7 Aug 2021 | 43-2 v ReadingStoke City 3-2 Reading |
| 2 | Sat 14 Aug 2021 | 40-0 v Birmingham CityBirmingham City 0-0 Stoke City |
| 3 | Tue 17 Aug 2021 | 43-1 v Swansea CitySwansea City 1-3 Stoke City |
| 4 | Sat 21 Aug 2021 | 41-0 v Nottingham ForestStoke City 1-0 Nottingham Forest |
| 5 | Sat 28 Aug 2021 | 40-3 v FulhamFulham 3-0 Stoke City |
| 6 | Sat 11 Sep 2021 | 4 2-1 v Huddersfield TownStoke City 2-1 Huddersfield Town |
| 7 | Wed 15 Sep 2021 | 41-1 v BarnsleyStoke City 1-1 Barnsley |
| 8 | Fri 1 Oct 2021 | 41-0 v West Bromwich AlbionStoke City 1-0 West Bromwich Albion |
| 9 | Sat 16 Oct 2021 | 41-2 v Sheffield UnitedSheffield United 2-1 Stoke City |
| 10 | Sat 23 Oct 2021 | 41-2 v MillwallMillwall 2-1 Stoke City |
| 11 | Sat 30 Oct 2021 | 43-3 v Cardiff CityStoke City 3-3 Cardiff City |
| 12 | Wed 3 Nov 2021 | 41-0 v BlackpoolBlackpool 0-1 Stoke City |
| 13 | Sat 6 Nov 2021 | 41-0 v Luton TownLuton Town 0-1 Stoke City |
| 14 | Sat 20 Nov 2021 | 4 2-0 v Peterborough UnitedStoke City 2-0 Peterborough United |
| 15 | Wed 24 Nov 2021 | 4 0-1 v Bristol CityBristol City 1-0 Stoke City |
| 16 | Sun 5 Dec 2021 | 42-0 v Queens Park RangersQueens Park Rangers 0-2 Stoke City |
| 17 | Sat 11 Dec 2021 | 40-0 v MiddlesbroughStoke City 0-0 Middlesbrough |
| 18 | Thu 30 Dec 2021 | 41-2 v Derby CountyStoke City 1-2 Derby County |
| 19 | Mon 3 Jan 2022 | 4 1-2 v Preston North EndStoke City 1-2 Preston North End |
| 20 | Sun 16 Jan 2022 | 42-0 v Hull CityHull City 0-2 Stoke City |
| 21 | Sat 22 Jan 2022 | 42-3 v FulhamStoke City 2-3 Fulham |
| 22 | Tue 25 Jan 2022 | 40-1 v Coventry CityCoventry City 1-0 Stoke City |
| 23 | Fri 28 Jan 2022 | 41-1 v Huddersfield TownHuddersfield Town 1-1 Stoke City |
| 24 | Tue 8 Feb 2022 | 43-0 v Swansea CityStoke City 3-0 Swansea City |
| 25 | Sat 12 Feb 2022 | 4 2-2 v Nottingham ForestNottingham Forest 2-2 Stoke City |
| 26 | Sat 19 Feb 2022 | 42-2 v Birmingham CityStoke City 2-2 Birmingham City |
| 27 | Wed 23 Feb 2022 | 41-2 v Luton TownStoke City 1-2 Luton Town |
| 28 | Sat 26 Feb 2022 | 41-2 v AFC BournemouthAFC Bournemouth 2-1 Stoke City |
| 29 | Tue 8 Mar 2022 | 41-1 v BarnsleyBarnsley 1-1 Stoke City |
| 30 | Sat 12 Mar 2022 | 4 2-2 v Peterborough UnitedPeterborough United 2-2 Stoke City |
| 31 | Wed 16 Mar 2022 | 41-2 v Cardiff CityCardiff City 2-1 Stoke City |
| 32 | Sat 19 Mar 2022 | 42-0 v MillwallStoke City 2-0 Millwall |
| 33 | Sat 2 Apr 2022 | 41-0 v Sheffield UnitedStoke City 1-0 Sheffield United |
| 34 | Tue 5 Apr 2022 | 41-2 v ReadingReading 2-1 Stoke City |
| 35 | Sat 9 Apr 2022 | 43-1 v West Bromwich AlbionWest Bromwich Albion 1-3 Stoke City |
| 36 | Fri 15 Apr 2022 | 40-1 v Bristol CityStoke City 0-1 Bristol City |
| 37 | Mon 18 Apr 2022 | 41-0 v Blackburn RoversBlackburn Rovers 0-1 Stoke City |
| 38 | Sat 23 Apr 2022 | 41-0 v Queens Park RangersStoke City 1-0 Queens Park Rangers |
| 39 | Sat 30 Apr 2022 | 41-3 v MiddlesbroughMiddlesbrough 3-1 Stoke City |
| 40 | Sat 7 May 2022 | 41-1 v Coventry CityStoke City 1-1 Coventry City |
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