[1] The competition began on 7 August 2021 and concluded with the final at Windsor Park, Belfast on 7 May 2022.

[2] Linfield were the defending champions, having defeated Larne 2–1 in the previous season's final.

This was a large increase on the 26 entrants for the previous season's competition, which was played in a condensed format as a result of the COVID-19 pandemic in Northern Ireland.

The league tier of each club at the time of entering the competition is listed in parentheses.

The draw for the first qualifying round took place on 20 July 2021, with the matches played on 7 and 14 August 2021.

Mossley, originally drawn to face Wellington Recreation or Donegal Celtic, were given a bye into the third qualifying round after both clubs were dismissed from the competition.

However, the match between Newry City and Ballymena United was delayed as a result of Glentoran's appeal against their expulsion from the competition.

Ballymena United and Crusaders competed in an Irish Cup final for the first time.