| Opponents | | Date | Comp | Ven | F | A | GK | RB | CB | CB | LB | CM | CM | RM | AM | LM | A | Attnd | Spurs Goalscorers (mins) |
| Leyton Orient | 
| 17.07.21 | Friendly | A | 1 | 1 | Hart 45 | Paskotši 66 | Carter-Vickers 65 | Dier 65 | Cesay 65 | Winks 66 | John 66 | Moura 66 | Alli 65 | Bergwijn 66 | Scarlett 66 | N/A | Scarlett (38) |
| | | | | (1 | 0) | Whiteman 45 | Fagan-Walcott 24 | White 25 | Omole 25 | Eyoma 25 | Bowden 24 | Lyons-Foster 24 | Devine 24 | Parrott 25 | Mundle 24 | Clarke 24 | | |
| Colchester United | 
| 21.07.21 | Friendly | A | 3 | 0 | Whiteman | Carter-Vickers 66 | Dier 45 | Paskotši 66 | Omole 66 | Skipp 45 | Winks 66 | Bergwijn 66 | Alli 66 | Moura 66 | Son 45 | N/A | Son (11), Moura (14), Alli (38) |
| | | | | (3 | 0) | | Cesay 24 | Tanganga 45 | Lyons-Foster 24 | Fagan-Walcott 24 | John 45 | White 24 | Clarke 24 | Devine 24 | Parrott 24 | Scarlett 45 | | |
| Milton Keynes Dons | 
| 28.07.21 | Friendly | A | 3 | 1 | Whiteman | Doherty 63 | Tanganga 86 | Carter-Vickers | Reguilon 63 | Skipp 74 | John | Moura 82 | Alli 82 | Bergwijn 82 | Son 74 | N/A | Son (35), Alli (57), Moura (80) |
| | | | | (1 | 0) | | Paskotši 27 | Fagan-Walcott 4 | | Davies 27 | Omole 16 | | Clarke 8 | White 8 | Parrott 8 | Scarlett 16 | | |
| Chelsea | 
| 04.08.21 | Mind Series | A | 2 | 2 | Gollini | Doherty 80 | Tanganga | Dier | Reguilón 73 | Skipp | Højbjerg 45 | Bergwijn 80 | Alli | Moura | Son | | Moura (56), Bergwijn (70) |
| | | | | (0 | 1) | | Aurier 10 | | | Davies 17 | | Winks 45 | Scarlett 10 | | | | | |
| Arsenal | 
| 08.08.21 | Mind Series | H | 1 | 0 | Lloris 68 | Tanganga 87 | Sánchez 73 | Dier | Reguilón | Skipp 84 | Højbjerg 68 | Bergwijn | Alli | Moura | Son 84 | | Son (79) |
| | | | | (0 | 0) | Gollini 22 | Aurier 3 | Rodon 17 | | | Winks 6 | Lo Celso 22 | | | | Scarlett 6 | | |
| Manchester City | 
| 15.08.21 | PL 1 | H | 1 | 0 | Lloris | Tanganga 83 | Sánchez | Dier | Reguilón | Skipp | Højbjerg 89 | Bergwijn 77 | Alli | Moura | Son | 58,262 | Son (55) |
| | | | | (0 | 0) | | Doherty 7 | | | | | Romero 1 | Lo Celso 13 | | | | | |
| Paços de Ferreira (Portugal) | 
| 19.08.21 | UEFA Conf | A | 0 | 1 | Gollini | Carter-Vickers 87 | Romero | Davies | Doherty | Lo Celso | Winks | Sessegnon 80 | John 45 | Gil | Scarlett | 2,284 | X |
| | | PO L1 | | (0 | 1) | | Paskotši 3 | | | | | | Bennett 10 | Clarke 45 | | | | |
| Wolverhampton Wanderers | 
| 22.08.21 | PL 2 | A | 1 | 0 | Lloris | Tanganga | Sánchez | Dier | Reguilón | Skipp | Højbjerg | Bergwijn 89 | Alli | Moura 67 | Son 72 | 30,368 | Alli (pen 9) |
| | | | | (1 | 0) | | | | | | | | Winks 1 | | Lo Celso 23 | Kane 18 | | |
| Paços de Ferreira (Portugal) | 
| 26.08.21 | UEFA Conf | H | 3 | 0 | Gollini | Dier | Romero | Davies | Doherty | Lo Celso | Winks | Sessegnon 63 | Moura 84 | Gil 73 | Kane 72 | 30,215 | Kane (8, 34), Lo Celso (70) |
| | | PO L2 | | (2 | 0) | | | | | | | | Højbjerg 27 | Alli 6 | Bergwijn 17 | Son 18 | | |
| Watford | 
| 29.08.21 | PL 3 | H | 1 | 0 | Lloris | Tanganga | Sánchez | Dier | Reguilón | Skipp | Højbjerg | Bergwijn 68 | Alli | Son 88 | Kane | 57,672 | Son (42) |
| | | | | (1 | 0) | | | | | | | | Moura 22 | | Gil 2 | | | |
| Crystal Palace | 
| 11.09.21 | PL 4 | A | 0 | 3 | Lloris | Royal | Tanganga 58 | Dier 12 | Reguilón | Højbjerg | Skipp | Winks 60 | Moura | Kane | Alli | 22,740 | X |
| | | | | (0 | 0) | | | | Rodon 78 | | | | Davies 30 | | | | | |
| Rennes | 
| 16.09.21 | UEFA Conf | A | 2 | 2 | Gollini | Doherty | Tanganga | Rodon | Davies | Ndombele 78 | Skipp | Gil | Moura 54 | Kane 54 | Bergwijn 30 | 22,000 | Bade OG (11), Højbjerg (76) |
| (France) | | | GS 1 | | (1 | 1) | | | | | | Alli 12 | | | Scarlett 36 | Royal 36 | Højbjerg 60 | | |
| Chelsea | 
| 19.09.21 | PL 5 | H | 0 | 3 | Lloris | Royal | Dier | Romero 83 | Reguilón | Højbjerg | Lo Celso 62 | Ndombele 62 | Alli | Son | Kane | 60,059 | X |
| | | | | (0 | 0) | | | | Sánchez 7 | | | Gill 28 | Skipp 28 | | | | | |
| Wolverhampton |

| 22.09.21 | LGE CUP | A | 2 | 2 | Gollini | Tanganga 89 | Romero | Sánchez | Davies | Skipp | Alli 82 | Gill | Ndombele | Lo Celso 62 | Kane | 28,798 | Ndombele (14), Kane (23) |
| Wanderers | | | R3 (pens 3-2) | | (2 | 1) | | Reguilón 1 | | | | | Højbjerg 8 | | | Son 28 | | | |
| Arsenal | 
| 26.09.21 | PL 6 | A | 1 | 3 | Lloris | Tanganga 45 | Sánchez | Dier | Reguilón | Højbjerg | Alli 45 | Moura | Ndombele 70 | Son | Kane | 59,919 | Son (79) |
| | | | | (0 | 3) | | Royal 45 | | | | | Skipp 45 | | Gil 20 | | | | |
| NŠ Mura | 
| 30.09.21 | UEFA Conf | H | 5 | 1 | Gollini | Doherty | Rodon | Romero | Reguilón 81 | Alli 60 | Skipp 69 | Winks | Lo Celso | Scarlett 59 | Gil 60 | 25,121 | Alli (pen 4), Lo Celso (8), Kane (68, 77, 88) |
| (Slovenia) | | | GS 2 | | (2 | 0) | | | | | Royal 9 | Son 30 | Højbjerg 21 | | | Kane 31 | Moura 30 | | |
| Aston Villa | 
| 02.10.21 | PL 7 | H | 2 | 1 | Lloris | Royal | Romero | Dier | Reguilón | Højbjerg | Skipp | Ndombele 76 | Moura 89 | Kane | Son | 53,076 | Højbjerg (27), Targett OG (71) |
| | | | | (1 | 0) | | | | | | | | Lo Celso 14 | Gil 1 | | | | |
| Newcastle United | 
| 16.10.21 | PL 8 | A | 3 | 2 | Lloris | Royal | Romero | Dier | Reguilón | Højbjerg | Skipp | Ndombele | Moura | Kane | Son | 52.214 | Ndombele (17), Kane (22), Son (45+4) |
| | | | | (3 | 1 | | | | | | | | | | | | | |
| Vitesse | 
| 21.10.21 | UEFA Conf | A | 0 | 1 | Gollini | Tanganga | Sánchez | Rodon | Davies | Winks | Lo Celso | Gil | Alli | Bergwijn | Scarlett 75 | 23,931 | X |
| (Netherlands) | | | GS 3 | | (0 | 0) | | | | | | | | | | | Markanday 15 | | |
| West Ham United | 
| 23.10.21 | PL 9 | A | 0 | 1 | Lloris | Royal | Romero | Dier | Reguilón 84 | Højbjerg | Skipp | Ndombele 84 | Moura 89 | Kane | Son | 59,924 | X |
| | | | | (0 | 0) | | | | | Gil 6 | | | Lo Celso 6 | Bergwijn 1 | | | | |
| Burnley |

| 27.10.21 | LGE CUP | A | 1 | 0 | Gollini | Royal | Sánchez | Romero | Davies | Højbjerg | Skipp 66 | Lo Celso 89 | Bergwijn 66 | Kane | Gil 24 | 14,637 | Moura (68) |
| | | R4 | | (0 | 0) | | | | | | | Ndombele 24 | Rodon 1 | Son 24 | | Moura 66 | | |
| Manchester United | 
| 30.10.21 | PL 10 | H | 0 | 3 | Lloris | Royal | Romero | Dier | Davies | Højbjerg | Skipp 66 | Lo Celso 73 | Moura 54 | Kane | Son | 60,356 | X |
| | | | | (0 | 1) | | | | | | | Ndombele 24 | Alli 17 | Bergwijn 36 | | | | |
| Vitesse | 
| 04.11.21 | UEFA Conf | H | 3 | 2 | Lloris | Romero 59 | Dier | Davies | Royal | Højbjerg 87 | Skipp 73 | Reguilón | Moura 73 | Kane | Son 72 | 36,312 | Son (14), Moura (22), Rasmussen OG (28) |
| (Netherlands) | | | GS 4 | | (3 | 2) | | | | | | Lo Celso 3 | Winks 17 | | Sánchez 17 | | Ndombele 18 | | |
| Everton | 
| 06.11.21 | PL 11 | A | 0 | 0 | Lloris | Romero | Dier | Davies | Royal | Højbjerg | Skipp | Reguilón 71 | Moura 71 | Kane | Son 85 | 39,059 | X |
| | | | | (0 | 0) | | | | | | | | Doherty 19 | Lo Celso 19 | | Ndombele 5 | | |
| Leeds United | 
| 20.11.21 | PL 12 | H | 2 | 1 | Lloris | Tanganga 68 | Dier | Davies | Royal | Højbjerg | Winks | Reguilón 79 | Moura 88 | Kane | Son | 58,989 | Højbjerg (58), Reguilón (69) |
| | | | | (0 | 1) | | Sánchez 22 | | | | | | Sessegnon 11 | Alli 2 | | | | |
| NŠ Mura | 
| 25.11.21 | UEFA Conf | A | 1 | 2 | Gollini | Tanganga | Rodon 54 | Sánchez | Doherty 53 | Skipp | Ndombele 76 | Sessegnon 31 | Alli 54 | Kane | Gil 54 | 6,100 | Kane (72) |
| (Slovenia) | | | GS 5 | | (0 | 1) | | | Dier 36 | | Davies 37 | | Højbjerg 14 | | Son 36 | | Moura 36 | | |
| Brentford | 
| 01.12.21 | PL 13 | H | 2 | 0 | Lloris | Sánchez | Dier | Davies | Royal 83 | Højbjerg | Skipp | Reguilón | Moura 77 | Kane | Son 87 | 54,202 | Canós OG (12), Son (65) |
| | | | | (1 | 0) | | | | | Tanganga 7 | | | | Winks 13 | | Bergwijn 3 | | |
| Norwich City | 
| 05.12.21 | PL 14 | H | 3 | 0 | Lloris | Sánchez | Dier | Davies | Tanganga 62 | Højbjerg | Skipp | Reguilón 22 | Moura 80 | Kane | Son | 57,088 | Moura (10), Sánchez (67), Son (77) |
| | | | | (1 | 0) | | | | | Doherty 28 | | | Sessegnon 68 | Bergwijn 10 | | | | |
| Liverpool | 
| 19.12.21 | PL 15 | H | 2 | 2 | Lloris | Sánchez | Dier | Davies | Royal | Winks | Alli 81 | Sessegnon 86 | Ndombele 64 | Kane | Son | 45,421 | Kane (13), Son (74) |
| | | | | (1 | 1) | | | | | | | Moura 9 | Reguilón 4 | Skipp 26 | | | | |
| West Ham United |

| 22.12.21 | LGE CUP | H | 2 | 1 | Lloris | Sánchez | Dier | Davies | Doherty 83 | Højbjerg | Skipp 77 | Reguilón 83 | Moura 61 | Kane | Bergwijn 61 | 40,031 | Bergwijn (29), Moura (34) |
| | | R5 | | (2 | 1) | | | | | Tanganga 7 | | Alli 13 | Royal 7 | Winks 29 | | Son 29 | | |
| Crystal Palace | 
| 26.12.21 | PL 16 | H | 3 | 0 | Lloris | Sánchez | Dier | Tanganga | Royal | Højbjerg 79 | Skipp | Reguilón | Moura | Kane 64 | Son 76 | 40,539 | Kane (32), Moura (34), Son (74) |
| | | | | (2 | 0) | | | | | | Ndombele 11 | | | | Bergwijn 26 | Gil 14 | | |
| Southampton | 
| 28.12.21 | PL 17 | A | 1 | 1 | Lloris | Sánchez | Dier | Davies | Royal 77 | Højbjerg | Winks | Reguilón 45 | Alli 62 | Kane | Son | 31,304 | Kane (pen 41) |
| Southampton | | | | | (1 | 1) | | | | | Gil 13 | | | Doherty 45 | Moura 28 | | | | |
| Watford | 
| 01.01.22 | PL 18 | A | 1 | 0 | Lloris | Sánchez | Dier | Davies | Royal | Højbjerg | Skipp 70 | Reguilón 83 | Moura 89 | Kane | Son | 20,391 | Sánchez (90+6) |
| | | | | (0 | 0) | | | | | | | Winks 20 | Lo Celso 7 | Gil 1 | | | | |
| Chelsea | 
| 05.01.22 | LGE CUP | A | 0 | 2 | Lloris | Tanganga | Sánchez | Davies | Royal | Højbjerg | Skipp 73 | Doherty 45 | Moura 80 | Kane | Son 79 | 37,868 | X |
| | | SF L1 | | (0 | 2) | | | | | | | Winks 17 | Ndombele 45 | Gil 10 | | Lo Celso 11 | | |
| Morecambe | 
| 09.01.21 | FA Cup | H | 3 | 1 | Gollini | Tanganga | Rodon | Davies | Doherty | Winks | Lo Celso 88 | Sessegnon 87 | Ndombele 69 | Alli 69 | Gil 69 | 40,310 | Winks (74), Moura (85), Kane (88) |
| | | R3 | | (0 | 1) | | | | | | | Scarlett 2 | Royal 3 | Skipp 21 | Kane 21 | Moura 21 | | |
| Chelsea | 
| 12.01.22 | LGE CUP | H | 0 | 1 | Gollini | Tanganga | Sánchez | Davies | Royal | Højbjerg | Winks 81 | Doherty 65 | Moura | Kane | Lo Celso 71 | 45,603 | X |
| | | SF L2 | | (0 | 1) | | | | | | | Skipp 9 | Sessegnon 25 | | | Gil 19 | | |
| Leicester City | 
| 19.01.22 | PL 19 | H | 3 | 2 | Lloris | Tanganga | Sánchez | Davies | Royal 45 | Højbjerg | Winks 74 | Skipp | Reguilón 79 | Moura | Kane | 31,986 | Kane (38), Begwijn (90+5, 90+7) |
| | | | | (1 | 1) | | | | | Doherty 45 | | Lo Celso 16 | | Bergwijn 11 | | | | |
| Chelsea | 
| 23.01.22 | PL 20 | A | 0 | 2 | Lloris | Tanganga 57 | Sánchez | Dier | Davies | Doherty | Højbjerg | Winks 89 | Sessegnon 56 | Kane | Bergwijn | 40,020 | X |
| | | | | (0 | 0) | | Skipp 33 | | | | | | Gil 1 | Moura 34 | | | | |
| Brighton & Hove | 
| 05.02.22 | FA Cup | H | 3 | 1 | Lloris | Sánchez | Romero 77 | Davies | Royal 87 | Højbjerg | Winks 77 | Reguilón | Moura 68 | Kane | Son 69 | 54,697 | Kane (13, 66) March OG (24) |
| Albion | | | R4 | | (2 | 0) | | | Rodon 13 | | Doherty 3 | | Bentancur 13 | | Kulusevski 22 | | Bergwijn 21 | | |
| Southampton | 
| 09.02.22 | PL 21 | H | 2 | 3 | Lloris | Sánchez | Romero | Davies | Royal | Højbjerg 60 | Winks | Reguilón 83 | Moura 76 | Kane | Son | 54,012 | Bednarek OG (18), Son (70) |
| | | | | (1 | 1) | | | | | | Bentancur 30 | | Bergwijn 7 | Kulusevski 14 | | | | Bednarek |
| Wolverhampton Wanderers |

| 13.02.22 | PL 22 | H | 0 | 2 | Lloris | Sánchez | Romero | Davies | Doherty 82 | Winks | Bentancur | Sessegnon 28 | Moura 71 | Kane | Son | 56,452 | X |
| | | | | (0 | 2) | | | | | Royal 8 | | | Kulusevski 62 | Bergwijn 19 | | | | |
| Manchester City | 
| 19.02.22 | PL 23 | A | 3 | 2 | Lloris | Romero | Dier | Davies | Royal 83 | Højbjerg | Bentancur | Sessegnon 89 | Kulusevski | Kane | Son 80 | 53,201 | Kulusevski (4), Kane (59, 95+5) |
| | | | | (1 | 1) | | | | | Doherty 7 | | | Sánchez 1 | | | Moura 10 | | |
| Burnley | 
| 23.02.22 | PL 24 | A | 0 | 1 | Lloris | Romero | Dier | Davies | Royal 65 | Højbjerg | Bentancur 45 | Sessegnon 79 | Kulusevski | Kane | Son | 19,488 | X |
| | | | | (0 | 0) | | | | | Moura 25 | | Winks 45 | Bergwijn 11 | | | | | |
| Leeds United | 
| 26.02.22 | PL 25 | A | 4 | 0 | Lloris | Romero | Dier | Davies | Doherty | Højbjerg | Winks | Sessegnon 78 | Kulusevski 78 | Kane | Son 87 | 36,599 | Doherty (10), Kulusevski (15), Kane (27), Son (85) |
| | | | | (3 | 0) | | | | | | | | Royal 12 | Bergwijn 12 | | Scarlett 3 | | |
| Middlesbrough | 
| 01.03.22 | FA Cup | A | 0 | 1 | Lloris | Romero | Dier | Davies 115 | Doherty 81 | Højbjerg | Winks | Sessegnon 81 | Kulusevski 105 | Kane | Son | 31,135 | X |
| | | R5 (AET) | | (0 | 0) | | | | Scarlett 5 | Royal 39 | | | Bergwijn 39 | Reguilón 15 | | | | |
| Everton | 
| 07.03.22 | PL 26 | H | 5 | 0 | Lloris | Romero 52 | Dier | Davies | Doherty | Højbjerg | Bentancur | Sessegnon 45 | Kulusevski | Kane | Son 67 | 56,647 | Keane OG (14), Son (17), Kane (37, 55), Reguilón (46) |
| | | | | 3 | 0 | | Sánchez 38 | | | | | | Reguilón 45 | | | Bergwijn 23 | | |
| Manchester United | 
| 12.03.22 | PL 27 | A | 2 | 3 | Lloris | Romero | Dier | Davies 87 | Doherty | Højbjerg | Bentancur 88 | Reguilón | Kulusevski 78 | Kane | Son | 73,458 | Kane (35 pen), Maguire OG (72) |
| | | | | (1 | 2) | | | | Bergwijn 3 | | | Winks 2 | | Moura 12 | | | 73,458 | |
| Brighton & Hove Albion | 
| 16.03.22 | PL 28 | A | 2 | 0 | Lloris | Romero | Dier | Davies | Doherty 80 | Højbjerg | Bentancur | Reguilón | Kulusevski 89 | Kane | Son 80 | 31,144 | Romero (37), Kane (57) |
| | | | | (1 | 0) | | | | | Royal 10 | | | | Bergwijn 1 | | Moura 10 | | |
| West Ham United | 
| 20.03.22 | PL 29 | H | 3 | 1 | Lloris | Romero | Dier | Davies | Doherty | Højbjerg | Bentancur | Reguilón 88 | Kulusevski 89 | Kane | Son 89 | 58,685 | Zouma OG (9), Son (24, 88) |
| | | | | (2 | 1) | | | | | | | | Royal 2 | Bergwijn 1 | | Moura 1 | | Zouma |
| Newcastle United | 
| 03.04.22 | PL 30 | H | 5 | 1 | Lloris | Romero | Dier | Davies | Royal 81 | Højbjerg | Bentancur 75 | Doherty | Kulusevski 76 | Kane | Son | 57,553 | Davies (43), Doherty (48), Son (54), Royal (63), Bergwijn (83) |
| | | | | (1 | 1) | | | | | Bergwijn 9 | | Winks 15 | | Moura 14 | | | | |
| Aston Villa | 
| 09.04.22 | PL 31 | A | 4 | 0 | Lloris | Romero | Dier | Davies | Royal | Højbjerg | Bentancur | Doherty 21 | Kulusevski 84 | Kane | Son 78 | 41,949 | Son (3, 66, 71), Kulusevski (50) |
| | | | | (1 | 0) | | | | | | | | Reguilón 69 | Bergwijn 6 | | Moura 12 | | |
| Brighton & Hove Albion | 
| 16.04.22 | PL 32 | H | 0 | 1 | Lloris | Romero | Dier | Davies | Royal | Højbjerg | Bentancur 72 | Reguilón | Kulusevski 64 | Kane | Son 88 | 58,685 | X |
| | | | | (0 | 0) | | | | | | | Winks 18 | | Moura 26 | | Bergwijn 2 | | |
| Brentford | 
| 23.04.22 | PL 33 | A | 0 | 0 | Lloris | Romero | Dier | Davies | Royal 86 | Højbjerg | Bentancur | Sessegnon 74 | Kulusevski | Kane | Son | 17,072 | X |
| | | | | (0 | 0) | | | | | Moura 4 | | | Sánchez 16 | | | | | |
| Leicester City | 
| 01.05.22 | PL 34 | H | 3 | 1 | Lloris | Romero | Dier | Davies | Royal | Højbjerg | Bentancur 82 | Sessegnon | Moura 55 | Kane | Son 82 | 59,482 | Kane (22), Son (60, 79) |
| | | | | (1 | 0) | | | | | | | Winks 8 | | Kulusevski 35 | | Bergwijn 8 | | |
| Liverpool | 
| 07.05.22 | PL 35 | A | 1 | 1 | Lloris | Romero | Dier | Davies | Royal | Højbjerg | Bentancur | Sessegnon 78 | Kulusevski 85 | Kane | Son 89 | 53,177 | Son (56) |
| | | | | (0 | 0) | | | | | | | | Sánchez 12 | Winks 5 | | Bergwijn 1 | | |
| Arsenal | 
| 12.05.22 | PL 36 | H | 3 | 0 | Lloris | Sánchez | Dier | Davies 82 | Royal | Højbjerg | Bentancur | Sessegnon | Kulusevski 72 | Kane | Son 72 | 62,027 | Kane (pen 22, 37), Son (47) |
| | | | | (2 | 0) | | | | Rodon 8 | | | | | Moura 18 | | Bergwijn 18 | | |
| Burnley | 
| 15.05.22 | PL 37 | H | 1 | 0 | Lloris | Sánchez | Dier | Davies | Royal 89 | Højbjerg | Bentancur | Sessegnon | Moura 79 | Kane | Son | 61,729 | Kane (pen 45+8) |
| | | | | (1 | 0) | | | | | Rodon 1 | | | | Kulusevski 11 | | | | |
| Norwich City | 
| 22.05.22 | PL 38 | A | 5 | 0 | Lloris | Sánchez | Dier | Davies | Royal 73 | Højbjerg | Bentancur 73 | Sessegnon | Kulusevski 68 | Kane | Son | | Kulusevski (16, 64), Kane (32), Son (70, 75) |
| Norwich City | | | | | (2 | 0) | | | | | Bergwijn 17 | | Winks 17 | | Moura 22 | | | | Kulusevski |