The first round was played by all the qualified teams, except for the four participants of the 2020–21 Supercopa de España. The ten winners from the previous preliminary round were paired with ten teams from La Liga. The remaining six teams and the 22 teams of the Segunda División were paired with the four Copa Federación semi-finalists, the fourteen teams that competed in the Tercera División and ten teams from Segunda B. Finally, the remaining 36 teams from Segunda B 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, with 112 participating teams, from 15 to 30 December 2020.