As across Spain, match times up to 31 October 2021 and from 27 March 2022 were CEST (UTC+2). Times on interim ("winter") days were CET (UTC+1). Matches played in the Canary Islands used the WET (UTC±00:00).
New entries: All qualified teams except the four participants in the Supercopa de España. Opponents seeding: Teams from La Liga faced teams from the lowest divisions. The four remaining teams faced teams from Segunda División B. Local team seeding: Match played at home of team in lower division. Knock-out tournament type:Single match.
Second round
3 December 2021
14–16 December 2021
28
60 → 32
Opponents seeding: Teams from lowest divisions faced La Liga teams. Local team seeding: Match played at home of team in lower division. Knock-out tournament type: Single match
Round of 32
17 December 2021
4–6 January 2022
16
32 → 16
New entries: Clubs participating in the Supercopa de España gained entry. Opponents seeding: Teams from lowest divisions faced La Liga teams. Local team seeding: Match played at home of team in lower division. Knock-out tournament type: Single match.
Round of 16
7 January 2022
15, 16, 19 & 20 January 2022
8
16 → 8
Opponents seeding: Teams from lowest divisions faced La Liga teams. Local team seeding: Match played at home of team in lower division. Knock-out tournament type: Single match.
Quarter-finals
21 January 2022
2 & 3 February 2022
4
8 → 4
Opponents seeding: Luck of the draw. Local team seeding: Match played at home of team in lower division. Knock-out tournament type: Single match.
Semi-finals
4 February 2022
9 & 10 February 2022
2
4 → 2
Opponents seeding: Luck of the draw. Local team seeding: Luck of the draw. Knock-out tournament type:Double match.
Segunda División B All teams of each one of the five promotion groups (C), all winning teams and the two second-placed teams of each one of the five promotion groups (D) of the 2020–21 season
Tercera División The best teams plus the best fourteen runners-up of each one of the thirty-six promotion groups (A) and (B) of the 2020–21 season
^ Jump up to: abcdAthletic Bilbao, Atlético Madrid, Barcelona and Real Madrid joined the tournament in the round of 32, as participants of the Supercopa de España.
^Laguna did not play its game in its main stadium Francisco Peraza, in San Cristóbal de La Laguna, as it did not meet the requirements to broadcast the match.
The first round was played by 112 of the 116 qualified teams, with the exceptions being the four participants of the 2021–22 Supercopa de España. The ten winners from the previous preliminary round were paired with ten teams from La Liga. The four Copa Federación semi-finalists with another four teams from La Liga and the last two La Liga teams with two teams from Segunda RFEF. Twenty-one teams from Segunda RFEF were paired with the twenty-one Segunda División teams, the last nine teams from Segunda RFEF were paired with nine Primera RFEF teams. Finally, the remaining twenty teams from Primera RFEF were paired between them. In the case of opponents from the same division, the home advantage was decided by whichever team was drawn first; otherwise, the match was held in the stadium of the lower division team. A total of 56 games were played from 30 November to 2 December 2021.
^Victoria played its game at Riazor, in La Coruña instead of their regular stadium San Pedro de Visma as it does not meet the requirements established by the Royal Spanish Football Federation.
^Laguna played its game at Heliodoro Rodríguez López, in Santa Cruz de Tenerife instead of their regular stadium Francisco Peraza in San Cristóbal de La Laguna as it does not meet the requirements established by the Royal Spanish Football Federation.
^Racing Rioja played its game at Las Gaunas, in Logroño instead of their regular stadium El Salvador as it does not meet the requirements established by the Royal Spanish Football Federation.
^Ceares played its game at El Molinón, in Gijón instead of their regular stadium La Cruz as it does not meet the requirements established by the Royal Spanish Football Federation.
^Ebro played its game at La Romareda, in Zaragoza instead of their regular stadium La Almozara as it does not meet the requirements established by the Royal Spanish Football Federation.
^Panadería Pulido played its game at Gran Canaria, in Las Palmas de Gran Canaria instead of their regular stadium San Mateo in Vega de San Mateo as it does not meet the requirements established by the Royal Spanish Football Federation.
^Alicante played its game at El Collao, in Alcoy instead of their regular stadium Antonio Solana in Alicante as it does not meet the requirements established by the Royal Spanish Football Federation.
^Huracán Melilla played its game at Álvarez Claro, in Melilla instead of their regular stadium La Espiguera as it does not meet the requirements established by the Royal Spanish Football Federation.
^Llanera played its game at Ganzábal, in Langreo instead of their regular stadium Pepe Quimarán in Posada de Llanera as it does not meet the requirements established by the Royal Spanish Football Federation.
^Villa de Fortuna played its game at Nueva Condomina, in Murcia instead of their regular stadium José Luis Belda in Fortuna as it does not meet the requirements established by the Royal Spanish Football Federation.
The draw was held on 3 December 2021 in the RFEF headquarters in Las Rozas. Teams were divided into 4 pots according to their division in the 2021–22 season. Matches were played at the stadiums of lower-ranked teams. A total of 28 games were played from 14 to 16 December 2021.
^Llanera played its game at Ganzábal, in Langreo instead of their regular stadium Pepe Quimarán in Posada de Llanera as it does not meet the requirements established by the Royal Spanish Football Federation.
The draw was held on 17 December 2021 in the RFEF headquarters in Las Rozas. The four participant teams of the 2021–22 Supercopa de España were drawn with the teams from the lowest category. After them, the remaining teams from the lowest categories faced the rest of La Liga teams. Matches were played at stadiums of lower-ranked teams.
^Rayo Majadahonda played its game at Wanda Metropolitano, in Madrid instead of their regular stadium Cerro del Espino in Majadahonda because the Royal Spanish Football Federation have granted permission for a ground change to facilitate more fans at the match.
The draw was held on 7 January 2022 in the RFEF headquarters in Las Rozas. Teams are divided into 3 pots according to their division in the 2021–22 season. When possible, matches will be played at the stadiums of lower-ranked teams. Otherwise, the first team drawn plays home. A total of 8 games will be played from 15 to 20 January 2022.
^The match was originally played on 15 January at 21:30, but was suspended in the 40th minute after Sevilla's Joan Jordán was hit in the head by an object thrown from the crowd. The match was resumed the next day at 16:00 behind closed doors.
The draw was held on 21 January 2022 in the RFEF headquarters in Las Rozas. As there are no teams from the lower divisions, home teams were selected by a draw.
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