| 2021-12-28 | SouthamptonvTottenhamPremier League · England | 1–1 | Premier League · England |
| 2021-12-26 | West HamvSouthamptonPremier League · England | 2–3 | Premier League · England |
| 2021-12-15 | Crystal PalacevSouthamptonPremier League · England | 2–2 | Premier League · England |
| 2021-12-11 | ArsenalvSouthamptonPremier League · England | 3–0 | Premier League · England |
| 2021-12-04 | SouthamptonvBrightonPremier League · England | 1–1 | Premier League · England |
| 2021-12-01 | SouthamptonvLeicesterPremier League · England | 2–2 | Premier League · England |
| 2021-11-27 | LiverpoolvSouthamptonPremier League · England | 4–0 | Premier League · England |
| 2021-11-20 | NorwichvSouthamptonPremier League · England | 2–1 | Premier League · England |
| 2021-11-05 | SouthamptonvAston VillaPremier League · England | 1–0 | Premier League · England |
| 2021-10-30 | WatfordvSouthamptonPremier League · England | 0–1 | Premier League · England |
| 2021-10-23 | SouthamptonvBurnleyPremier League · England | 2–2 | Premier League · England |
| 2021-10-16 | SouthamptonvLeedsPremier League · England | 1–0 | Premier League · England |
| 2021-10-02 | ChelseavSouthamptonPremier League · England | 3–1 | Premier League · England |
| 2021-09-26 | SouthamptonvWolvesPremier League · England | 0–1 | Premier League · England |
| 2021-09-18 | Man CityvSouthamptonPremier League · England | 0–0 | Premier League · England |
| 2021-09-11 | SouthamptonvWest HamPremier League · England | 0–0 | Premier League · England |
| 2021-08-28 | NewcastlevSouthamptonPremier League · England | 2–2 | Premier League · England |
| 2021-08-22 | SouthamptonvMan UnitedPremier League · England | 1–1 | Premier League · England |
| 2021-08-14 | EvertonvSouthamptonPremier League · England | 3–1 | Premier League · England |
| 2021-05-23 | West HamvSouthamptonPremier League · England | 3–0 | Premier League · England |
| 2021-05-18 | SouthamptonvLeedsPremier League · England | 0–2 | Premier League · England |
| 2021-05-15 | SouthamptonvFulhamPremier League · England | 3–1 | Premier League · England |
| 2021-05-11 | SouthamptonvCrystal PalacePremier League · England | 3–1 | Premier League · England |
| 2021-05-08 | LiverpoolvSouthamptonPremier League · England | 2–0 | Premier League · England |
| 2021-04-30 | SouthamptonvLeicesterPremier League · England | 1–1 | Premier League · England |
| 2021-04-21 | TottenhamvSouthamptonPremier League · England | 2–1 | Premier League · England |
| 2021-04-12 | West BromvSouthamptonPremier League · England | 3–0 | Premier League · England |
| 2021-04-04 | SouthamptonvBurnleyPremier League · England | 3–2 | Premier League · England |
| 2021-03-14 | SouthamptonvBrightonPremier League · England | 1–2 | Premier League · England |
| 2021-03-10 | Man CityvSouthamptonPremier League · England | 5–2 | Premier League · England |
| 2021-03-06 | Sheffield UnitedvSouthamptonPremier League · England | 0–2 | Premier League · England |
| 2021-03-01 | EvertonvSouthamptonPremier League · England | 1–0 | Premier League · England |
| 2021-02-23 | LeedsvSouthamptonPremier League · England | 3–0 | Premier League · England |
| 2021-02-20 | SouthamptonvChelseaPremier League · England | 1–1 | Premier League · England |
| 2021-02-14 | SouthamptonvWolvesPremier League · England | 1–2 | Premier League · England |
| 2021-02-06 | NewcastlevSouthamptonPremier League · England | 3–2 | Premier League · England |
| 2021-02-02 | Man UnitedvSouthamptonPremier League · England | 9–0 | Premier League · England |
| 2021-01-30 | SouthamptonvAston VillaPremier League · England | 0–1 | Premier League · England |
| 2021-01-26 | SouthamptonvArsenalPremier League · England | 1–3 | Premier League · England |
| 2021-01-16 | LeicestervSouthamptonPremier League · England | 2–0 | Premier League · England |
| 2021-01-04 | SouthamptonvLiverpoolPremier League · England | 1–0 | Premier League · England |