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.
Note: Flags indicate national team as defined under FIFA eligibility rules; some limited exceptions apply. Players may hold more than one non-FIFA nationality.
^ abSince the 2021–22 DFB-Pokal winners, RB Leipzig, qualified for the Champions League based on league position, the Europa League group stage spot was passed to the sixth-placed team, and the Europa Conference League play-off round spot was passed to the seventh-placed team.