2021 AFC Champions League knockout stage
The 2021 AFC Champions League knockout stage was played from 13 September to 23 November 2021. A total of 16 teams competed in the knockout stage to decide the champions of the 2021 AFC Champions League.
Qualified teams
The group winners and three best runners-up in the group stage from each region advanced to the round of 16, with both West Region and East Region having eight qualified teams.| Region | Group | Winners | Runners-up |
| West Region | A | Istiklol | Al-Hilal |
| West Region | B | Sharjah | Tractor |
| West Region | C | Esteghlal | — |
| West Region | D | Al-Nassr | — |
| West Region | E | Persepolis | Al-Wahda |
| East Region | F | Ulsan Hyundai | BG Pathum United |
| East Region | G | Nagoya Grampus | Pohang Steelers |
| East Region | H | Jeonbuk Hyundai Motors | — |
| East Region | I | Kawasaki Frontale | Daegu FC |
| East Region | J | Cerezo Osaka | — |
Combination table
If two group winners played each other, the group winner marked with * hosted the match.;West Region
One-leg matches
| Qualified | 1A vs | 1B vs | 1C vs | 1D vs | 1E vs |
| 2A/2B/2C | 1B* | 1A | 2A | 2B | 2C |
| 2A/2B/2D | 1D | 2D | 2A | 1A* | 2B |
| 2A/2B/2E | 1E | 2E | 2A | 2B | 1A* |
| 2A/2C/2D | 1C* | 2D | 1A | 2A | 2C |
| 2A/2C/2E | 2C | 2E | 1E* | 2A | 1C |
| 2A/2D/2E | 2D | 2E | 2A | 1E* | 1D |
| 2B/2C/2D | 2D | 1C* | 1B | 2B | 2C |
| 2B/2C/2E | 2C | 1E | 2E | 2B | 1B* |
| 2B/2D/2E | 2D | 1D* | 2E | 1B | 2B |
| 2C/2D/2E | 2D | 2E | 1D* | 1C | 2C |
;East Region
One-leg matches
| Qualified | 1F vs | 1G vs | 1H vs | 1I vs | 1J vs |
| 2F/2G/2H | 1G* | 1F | 2F | 2G | 2H |
| 2F/2G/2I | 1I | 2I | 2F | 1F* | 2G |
| 2F/2G/2J | 1J | 2J | 2F | 2G | 1F* |
| 2F/2H/2I | 1H* | 2I | 1F | 2F | 2H |
| 2F/2H/2J | 2H | 2J | 1J* | 2F | 1H |
| 2F/2I/2J | 2I | 2J | 2F | 1J* | 1I |
| 2G/2H/2I | 2I | 1H* | 1G | 2G | 2H |
| 2G/2H/2J | 2H | 1J | 2J | 2G | 1G* |
| 2G/2I/2J | 2I | 1I* | 2J | 1G | 2G |
| 2H/2I/2J | 2I | 2J | 1I* | 1H | 2H |
Format
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. Extra time and penalty shoot-out were used to decide the winners if necessary.
Schedule
The schedule of each round was as follows.| Round | Date |
| Round of 16 | 13–15 September 2021 |
| Quarter-finals | 16–17 October 2021 |
| Semi-finals | 19–20 October 2021 |
| Final | 23 November 2021 |
Bracket
The bracket of the knockout stage was determined as follows:| Round | Format |
| Round of 16 | Matchups within East region and West region decided by a series of permutations, based upon the three best runner-ups who qualified |
| Quarter-finals | Matchups decided by a draw
|
| Semi-finals | |
| Final |
Round of 16
Summary
The round of 16 was played over one leg, with the matchups determined by the combination tables based on which group runners-up qualified.
West Region
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East Region
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Quarter-finals
Summary
The quarter-finals were played over one leg, with the matchups and home team decided by draw held on 17 September at 15:00 in Kuala Lumpur, Malaysia.
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West Region
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----Semi-finals
Summary
The semi-finals were played over one leg.
Final
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.