| 1 | Sat 12 Sep 2020 | 80-1 v Crystal PalaceCrystal Palace 1-0 Southampton |
| 2 | Sun 20 Sep 2020 | 8 2-5 v Tottenham HotspurSouthampton 2-5 Tottenham Hotspur |
| 3 | Sat 26 Sep 2020 | 81-0 v BurnleyBurnley 0-1 Southampton |
| 4 | Sun 4 Oct 2020 | 82-0 v West Bromwich AlbionSouthampton 2-0 West Bromwich Albion |
| 5 | Sat 17 Oct 2020 | 83-3 v ChelseaChelsea 3-3 Southampton |
| 6 | Sun 25 Oct 2020 | 82-0 v EvertonSouthampton 2-0 Everton |
| 7 | Sun 1 Nov 2020 | 8 4-3 v Aston VillaAston Villa 3-4 Southampton |
| 8 | Fri 6 Nov 2020 | 82-0 v Newcastle UnitedSouthampton 2-0 Newcastle United |
| 9 | Mon 23 Nov 2020 | 81-1 v Wolverhampton WanderersWolverhampton Wanderers 1-1 Southampton |
| 10 | Sun 29 Nov 2020 | 8 2-3 v Manchester UnitedSouthampton 2-3 Manchester United |
| 11 | Mon 7 Dec 2020 | 82-1 v Brighton & Hove AlbionBrighton & Hove Albion 1-2 Southampton |
| 12 | Sun 13 Dec 2020 | 83-0 v Sheffield UnitedSouthampton 3-0 Sheffield United |
| 13 | Wed 16 Dec 2020 | 81-1 v ArsenalArsenal 1-1 Southampton |
| 14 | Sat 19 Dec 2020 | 8 0-1 v Manchester CitySouthampton 0-1 Manchester City |
| 15 | Sat 26 Dec 2020 | 80-0 v FulhamFulham 0-0 Southampton |
| 16 | Tue 29 Dec 2020 | 80-0 v West Ham UnitedSouthampton 0-0 West Ham United |
| 17 | Mon 4 Jan 2021 | 81-0 v LiverpoolSouthampton 1-0 Liverpool |
| 18 | Sat 16 Jan 2021 | 80-2 v Leicester CityLeicester City 2-0 Southampton |
| 19 | Tue 26 Jan 2021 | 81-3 v ArsenalSouthampton 1-3 Arsenal |
| 20 | Sat 30 Jan 2021 | 8 0-1 v Aston VillaSouthampton 0-1 Aston Villa |
| 21 | Tue 2 Feb 2021 | 80-9 v Manchester UnitedManchester United 9-0 Southampton |
| 22 | Sat 6 Feb 2021 | 82-3 v Newcastle UnitedNewcastle United 3-2 Southampton |
| 23 | Sun 14 Feb 2021 | 81-2 v Wolverhampton WanderersSouthampton 1-2 Wolverhampton Wanderers |
| 24 | Sat 20 Feb 2021 | 81-1 v ChelseaSouthampton 1-1 Chelsea |
| 25 | Tue 23 Feb 2021 | 80-3 v Leeds UnitedLeeds United 3-0 Southampton |
| 26 | Mon 1 Mar 2021 | 80-1 v EvertonEverton 1-0 Southampton |
| 27 | Sat 6 Mar 2021 | 82-0 v Sheffield UnitedSheffield United 0-2 Southampton |
| 28 | Wed 10 Mar 2021 | 82-5 v Manchester CityManchester City 5-2 Southampton |
| 29 | Sun 14 Mar 2021 | 81-2 v Brighton & Hove AlbionSouthampton 1-2 Brighton & Hove Albion |
| 30 | Sun 4 Apr 2021 | 83-2 v BurnleySouthampton 3-2 Burnley |
| 31 | Mon 12 Apr 2021 | 8 0-3 v West Bromwich AlbionWest Bromwich Albion 3-0 Southampton |
| 32 | Wed 21 Apr 2021 | 81-2 v Tottenham HotspurTottenham Hotspur 2-1 Southampton |
| 33 | Fri 30 Apr 2021 | 81-1 v Leicester CitySouthampton 1-1 Leicester City |
| 34 | Sat 8 May 2021 | 80-2 v LiverpoolLiverpool 2-0 Southampton |
| 35 | Tue 11 May 2021 | 83-1 v Crystal PalaceSouthampton 3-1 Crystal Palace |
| 36 | Sat 15 May 2021 | 83-1 v FulhamSouthampton 3-1 Fulham |
| 37 | Tue 18 May 2021 | 80-2 v Leeds UnitedSouthampton 0-2 Leeds United |
| 38 | Sun 23 May 2021 | 80-3 v West Ham UnitedWest Ham United 3-0 Southampton |
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