The 2021 AFC Champions League knockout stage was played from 13 September to 23 November 2021.
[4] Extra time and penalty shoot-out were used to decide the winners if necessary (Regulations Article 9.3 and 10.1).
[1] The bracket of the knockout stage was determined as follows: Matchups within East region and West region decided by a series of permutations,based upon the three best runner-ups who qualified
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.