Juventus U23 were the defending champions having won their first title in June 2020 against Ternana, with a 2–1 final score in the final.
[1] The 2020–21 season was not held due to the COVID-19 pandemic.
[2] The 60 teams in the 2021–22 Serie C entered the competition at various stages, as follows:[3] The schedule of each rounds were announced on 27 July 2021.
[5] The round is contested by the winners of the previous round and the four teams that participated in the 2021–22 Coppa Italia.
Statistics include the goals scored by Pro Patria and Lucchese against FeralpiSalò and Legnago, for a total of 154 goals.