The 2021 AFC Champions League was the 40th edition of Asia's premier club football tournament organized by the Asian Football Confederation (AFC), and the 19th under the current AFC Champions League title.
 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. As winners, they automatically qualified for the 2022 AFC Champions League (although they had already qualified through their domestic performance). They also earned the right to play in the 2021 FIFA Club World Cup in the United Arab Emirates and the 2025 FIFA Club World Cup.
 The tournament was the first to involve 40 teams during the group stage, with an increase from the previous 32 teams.
 Ulsan Hyundai of South Korea were the defending champions, but were eliminated in the semi-finals by fellow South Korean club Pohang Steelers.
 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). The slots are allocated by the following criteria according to the Entry Manual:
 For the 2021 AFC Champions League, the associations are allocated slots according to their association ranking which was published on 29 November 2019, which takes into account their performance in the AFC Champions League and the AFC Cup during the period between 2016 and 2019.
  
 In the following table, the number of appearances and last appearance count only those since the 2002–03 season (including qualifying rounds), when the competition was rebranded as the AFC Champions League.
  
 The schedule of the competition is as follows.
 On 25 January 2021, the AFC published the schedule of the competition. The group stage is played as centralized double round-robin tournament, and the round of 16 and quarter-finals are played as a single match.
 Notes:
 The original schedule of the competition, as planned before the pandemic, was as follows.
 In the qualifying play-offs, each tie was played as a single match. Extra time and penalty shoot-out were used to decide the winner if necessary.
The bracket of the qualifying play-offs for each region was determined based on each team's association ranking and their seeding within their association, with the team from the higher-ranked association hosting the match in the West Region. Teams from the same association could not be placed into the same tie. The eight winners of the play-off round (four each from both West Region and East Region) advanced to the group stage to join the 32 direct entrants.
 The draw for the group stage was held at the AFC House in Kuala Lumpur, Malaysia, on 27 January 2021. The 40 teams were drawn into ten groups of four: five groups each in the West Region (Groups A–E) and the East Region (Groups F–J). For each zone, teams were seeded into four pots and drawn into the relevant positions within each group, based on their association ranking and their seeding within their association, in consideration of technical balance between groups. Teams from the same association could not be drawn into the same group.
 In the group stage, each group was played on a double round-robin basis in centralised venues. The winners of each group and three best runners-up from each region advanced to the round of 16 of the knockout stage.
 The teams were ranked according to points (3 points for a win, 1 point for a draw, 0 points for a loss). If tied on points, tiebreakers were applied in the following order (Regulations Article 8.3):
 In the knockout stage, the 16 teams played a single-elimination tournament, with the teams split into the two regions until the final. All ties were played as a single-leg match (Regulations Article 9.1). Extra time and penalty shoot-out were used to decide the winners if necessary (Regulations Article 9.3 and 10.1).
 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.
 
 The semi-finals were played over one leg.
 The final was played over a single leg on 23 November. The host was determined on a rotational basis, with the match hosted by team from the West Region in odd-numbered years (Regulations 9.1.2).
 Note: Goals scored in the qualifying play-offs and matches voided by AFC are not counted when determining top scorer (Regulations Article 64.4).