American team Seattle Sounders FC won its first CONCACAF Champions League title, defeating Mexican club UNAM 5–2 on aggregate in the final.

The Sounders thus became the first team from Major League Soccer to win the title under its current format.

[2] In the following table, the number of appearances, last appearance, and previous best result count only those in the CONCACAF Champions League era starting from 2008–09 (not counting those in the era of the Champions' Cup from 1962 to 2008).

Notes; The draw for the 2022 CONCACAF Champions League was held on 15 December 2021, in Miami, Florida, United States.

[6] The CONCACAF Club Index, instead of ranking each team, was based on the on-field performance of the teams that occupied the respective qualifying slots in the previous five editions of the CONCACAF Champions League.

To determine the total points awarded to a slot in any single edition of the CONCACAF Champions League, CONCACAF used the following formula: The slots were assigned by the following rules:[7] The 16 teams were distributed in the pots as follows:[8] Each tie, including the final, was played over two legs, with each team playing on a home-and-away basis.

New England Revolution advanced to the quarter-finals after Cavaly withdrew from the competition on 15 February 2022.

In the semi-finals, the matchups were determined as follows: The semi-finalists in each tie which had the better performance across all previous rounds hosted the second leg.

Winner SF2), the finalist which had the better performances in previous rounds hosted the second leg.