| Club: | 1. FSV Mainz 05 |
| Season: | 2021–22 |
| Chrtitle: | President |
| Chairman: | Stefan Hofmann |
| Mgrtitle: | Head coach |
| Manager: | Bo Svensson |
| Stadium: | Mewa Arena |
| League: | Bundesliga |
| League Result: | 8th |
| Cup1: | DFB-Pokal |
| Cup1 Result: | Round of 16 |
| League Topscorer: | Jonathan Burkardt (11) |
| Season Topscorer: | Jonathan Burkardt (14) |
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| Prevseason: | 2020–21 |
| Nextseason: | 2022–23 |
The 2021–22 season was the 117th season in the existence of 1. FSV Mainz 05 and the club's 13th consecutive season in the top flight of German football. In addition to the domestic league, Mainz participated in this season's edition of the DFB-Pokal.
| Date | Pos. | Name | To | Fee | ||
|---|---|---|---|---|---|---|
| 1 June 2021 | DF |  Phillipp Mwene | PSV | Free | [3] | |
| 1 June 2021 | MF | Danny Latza | Schalke 04 | Free | [4] | |
| 1 June 2021 | MF | Levin Öztunali | Union Berlin | Free | [5] | |
| 10 June 2021 | FW | Marlon Mustapha | Admira Wacker Mödling | Loan | [6] | |
| 10 June 2021 | GK | Florian Muller | VFB Stuttgart | €5 million | [7] | |
| 23 June 2021 | MF |  Pierre Kunde | Olympiacos F.C. | Undisclosed | [8] | |
| 29 June 2021 | MF |  Issah Abass | NK Rijeka | Loan | [9] | |
| 8 July 2021 | FW |  Ji Dong-Won | FC Seoul | Undisclosed | [10] | |
| 9 July 2021 | FW |  Robin Quaison | Al-Ettifaq | Undisclosed | [11] | |
| 14 August 2021 | DF | Jonathan Maier | Hansa Rostock | Loan | [12] | |
| 25 August 2021 | DF | Luca Killian | 1. FC Köln | Loan | [13] |
See main article: 2021–22 Bundesliga.
The league fixtures were announced on 25 June 2021.[14]
See main article: 2021–22 DFB-Pokal.