The 2021 AFC Cup qualifying play-offs were played from 7 April to 15 August 2021. A total of seven teams competed in the qualifying play-offs to decide three of the 38 places in the group stage of the 2021 AFC Cup.
The following 7 teams, split into five zones (West Asia Zone, Central Asia Zone, South Asia Zone, ASEAN Zone, East Asia Zone), entered the qualifying play-offs, consisting of three rounds:
<section begin=Format /> 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.<section end=Format />
The schedule of each round was as follows.
<section begin=Format /> The bracket of the qualifying play-offs for each zone was determined based on each team's association ranking, with the team from the higher-ranked association hosting the match. The one winner of preliminary round 2 (from ASEAN Zone) and one winner of the play-off round (from South Zone) advanced to the group stage to join the 35 direct entrants.<section end=Format />
A total of four teams played in the preliminary round 1. <section begin=Preliminary round 1/>
|+South Asia Zone
<section end=Preliminary round 1/>
A total of eight teams played in the preliminary round 2: six teams which entered in this round, and two winners of the preliminary round 1. <section begin=Preliminary round 2/>
|+South Asia Zone
|+ASEAN Zone
<section end=Preliminary round 2/>
A total of eight teams played in the play-off round: four teams which entered in this round, and four winners of the preliminary round 2. <section begin=Play-off round/>
|+West Asia Zone
|+South Asia Zone
|+ASEAN Zone
<section end=Play-off round/>