The 2021–22 season was Pisa S.C.'s third consecutive season in second division of the Italian football league, the Serie B, and the 113th as a football club.

Note: Flags indicate national team as defined under FIFA eligibility rules; some limited exceptions apply.

Players may hold more than one non-FIFA nationality.

Note: Flags indicate national team as defined under FIFA eligibility rules; some limited exceptions apply.

Win Draw Loss Source: Soccerway Source: Serie B The league fixtures were announced on 24 July 2021.