[2] Al-Hilal won their fourth title by defeating Pohang Steelers 2–0 in the final, becoming the most successful team in the history of the competition.

The 46 AFC member associations (excluding the Northern Mariana Islands, which became a full member in December 2020 and are not eligible for this season) are ranked based on their clubs' performance over the last four years in AFC competitions (their national team's FIFA World Rankings no longer considered).

[36] The draw for the group stage was held at the AFC House in Kuala Lumpur, Malaysia, on 27 January 2021.

[41] Extra time and penalty shoot-out were used to decide the winners if necessary (Regulations Article 9.3 and 10.1).

[2] The round of 16 was played over one leg, with the matchups determined by the combination tables based on which group runners-up qualified.

The quarter-finals were played over one leg, with the matchups and home team decided by draw held on 17 September at 15:00 (UTC+8) in Kuala Lumpur, Malaysia.

[2] Note: Goals scored in the qualifying play-offs and matches voided by AFC are not counted when determining top scorer (Regulations Article 64.4).