| 1 | Sat 21 Aug 2021 | 5 0-2 v VfL BochumVfL Bochum 2-0 Mainz 05 | German Bundesliga |
| 2 | Sat 28 Aug 2021 | 53-0 v Greuther FürthMainz 05 3-0 Greuther Fürth | German Bundesliga |
| 3 | Sat 11 Sep 2021 | 52-0 v 1899 Hoffenheim1899 Hoffenheim 0-2 Mainz 05 | German Bundesliga |
| 4 | Sat 18 Sep 2021 | 50-0 v SC FreiburgMainz 05 0-0 SC Freiburg | German Bundesliga |
| 5 | Sat 25 Sep 2021 | 50-1 v Bayer 04 LeverkusenBayer 04 Leverkusen 1-0 Mainz 05 | German Bundesliga |
| 6 | Sun 3 Oct 2021 | 51-2 v 1. FC Union BerlinMainz 05 1-2 1. FC Union Berlin | German Bundesliga |
| 7 | Sat 16 Oct 2021 | 51-3 v Borussia DortmundBorussia Dortmund 3-1 Mainz 05 | German Bundesliga |
| 8 | Fri 22 Oct 2021 | 54-1 v FC AugsburgMainz 05 4-1 FC Augsburg | German Bundesliga |
| 9 | Sat 30 Oct 2021 | 52-1 v Arminia BielefeldArminia Bielefeld 1-2 Mainz 05 | German Bundesliga |
| 10 | Fri 5 Nov 2021 | 5 1-1 v Borussia MönchengladbachMainz 05 1-1 Borussia Mönchengladbach | German Bundesliga |
| 11 | Sun 21 Nov 2021 | 51-1 v 1. FC KölnMainz 05 1-1 1. FC Köln | German Bundesliga |
| 12 | Fri 26 Nov 2021 | 5 1-2 v VfB StuttgartVfB Stuttgart 2-1 Mainz 05 | German Bundesliga |
| 13 | Sat 4 Dec 2021 | 53-0 v VfL WolfsburgMainz 05 3-0 VfL Wolfsburg | German Bundesliga |
| 14 | Sat 11 Dec 2021 | 51-2 v Bayern MunichBayern Munich 2-1 Mainz 05 | German Bundesliga |
| 15 | Tue 14 Dec 2021 | 54-0 v Hertha BerlinMainz 05 4-0 Hertha Berlin | German Bundesliga |
| 16 | Sat 18 Dec 2021 | 50-1 v Eintracht FrankfurtEintracht Frankfurt 1-0 Mainz 05 | German Bundesliga |
| 17 | Sat 8 Jan 2022 | 51-4 v RB LeipzigRB Leipzig 4-1 Mainz 05 | German Bundesliga |
| 18 | Sat 15 Jan 2022 | 51-0 v VfL BochumMainz 05 1-0 VfL Bochum | German Bundesliga |
| 19 | Sat 22 Jan 2022 | 51-2 v Greuther FürthGreuther Fürth 2-1 Mainz 05 | German Bundesliga |
| 20 | Sat 5 Feb 2022 | 52-0 v 1899 HoffenheimMainz 05 2-0 1899 Hoffenheim | German Bundesliga |
| 21 | Sat 12 Feb 2022 | 51-1 v SC FreiburgSC Freiburg 1-1 Mainz 05 | German Bundesliga |
| 22 | Fri 18 Feb 2022 | 53-2 v Bayer 04 LeverkusenMainz 05 3-2 Bayer 04 Leverkusen | German Bundesliga |
| 23 | Sat 26 Feb 2022 | 51-3 v 1. FC Union Berlin1. FC Union Berlin 3-1 Mainz 05 | German Bundesliga |
| 24 | Wed 16 Mar 2022 | 50-1 v Borussia DortmundMainz 05 0-1 Borussia Dortmund | German Bundesliga |
| 25 | Sat 19 Mar 2022 | 54-0 v Arminia BielefeldMainz 05 4-0 Arminia Bielefeld | German Bundesliga |
| 26 | Sun 3 Apr 2022 | 51-1 v Borussia MönchengladbachBorussia Mönchengladbach 1-1 Mainz 05 | German Bundesliga |
| 27 | Wed 6 Apr 2022 | 51-2 v FC AugsburgFC Augsburg 2-1 Mainz 05 | German Bundesliga |
| 28 | Sat 9 Apr 2022 | 52-3 v 1. FC Köln1. FC Köln 3-2 Mainz 05 | German Bundesliga |
| 29 | Sat 16 Apr 2022 | 50-0 v VfB StuttgartMainz 05 0-0 VfB Stuttgart | German Bundesliga |
| 30 | Fri 22 Apr 2022 | 50-5 v VfL WolfsburgVfL Wolfsburg 5-0 Mainz 05 | German Bundesliga |
| 31 | Sat 30 Apr 2022 | 53-1 v Bayern MunichMainz 05 3-1 Bayern Munich | German Bundesliga |
| 32 | Sat 7 May 2022 | 52-1 v Hertha BerlinHertha Berlin 1-2 Mainz 05 | German Bundesliga |
| 33 | Sat 14 May 2022 | 52-2 v Eintracht FrankfurtMainz 05 2-2 Eintracht Frankfurt | German Bundesliga |
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