[1] Comunicaciones defeated Motagua in the final to win their first CONCACAF League title.

As winners, they and the next best five teams qualified for the 2022 CONCACAF Champions League.

[2][3] Alajuelense were the title holders but were eliminated by Guastatoya in the Round of 16.

The one berth for the North American Zone (NAFU) was allocated to the Canadian Soccer Association through the previous year's Canadian Premier League, where the champions, decided by the Canadian Premier League Finals contested between the top two teams of the group stage, qualified.

[4] They are the second Canadian representative included in CONCACAF competitions, besides the Canadian Championship champions which qualify for the CONCACAF Champions League.

All of the leagues of Central America employ a split season with two tournaments in one season, so the following teams qualified for the CONCACAF League: If teams from any Central American associations were excluded, they would be replaced by teams from other Central American associations, with the associations chosen based on results from previous CONCACAF League and CONCACAF Champions League tournaments.

Since 2018, the CONCACAF Caribbean Club Championship is open to teams from professional leagues, where they can qualify as champions or runners-up of their respective association's league in the previous season, while the CONCACAF Caribbean Club Shield is open to teams from non-professional leagues, where they can qualify as champions of their respective association's league in the previous season.

The six preliminary round winners, whose identity is not known at the time of the draw, are in Pot 4 and can be drawn into the same tie with another team from the same association.

The seeding of teams was based on the CONCACAF Club Index.

To determine the total points awarded to a slot in any single edition of the CONCACAF League or CONCACAF Champions League, CONCACAF uses the following formula: Teams qualified for the CONCACAF League based on criteria set by their association (e.g., tournament champions, runners-up, cup champions), resulting in an assigned slot (e.g., CRC1, CRC2) for each team.

Olimpia would be disqualified from the competition due to rule breaches following the first leg of their round of 16 fixture, including an alleged payment from Inter Moengotapoe owner and player Ronnie Brunswijk to several Olimpia players.

Inter Moengotapoe and Olimpia were disqualified from the tournament by CONCACAF due to rule breaches following the first leg match.

Based on the ranking, the top six teams, i.e., champions, runners-up, both losing semi-finalists, and best two losing quarter-finalists, qualify for the 2022 CONCACAF Champions League.