The competition began on 13 August 2021 with a single-fixture first round and concluded on 21 November 2021.
The Cup holders Peamount United were eliminated at the semi-final stage.
Women's National League (WNL) clubs Bohemians and DLR Waves were selected to play in a single match first round, the winner of which was to join the other seven WNL clubs in the quarter-finals.
Athlone Town, Galway and Treaty United received a bye to the quarter-finals, while the top four teams in the 2020 Women's National League (Peamount United, Shelbourne, Wexford Youths and Cork City) were exempt from the first round draw and qualified automatically for the quarter-finals.
[3] The draw for the semi-finals was made by Vera Pauw on 8 September 2021.