The top six placed teams from the top-tier level Greek Basket League's 2020–21 season, gained an automatic bye to the 2021–22 Greek Cup quarterfinals. While the seven lower-placed teams from the 2020–21 Greek Basket League season also gained an automatic bye to the 2021–22 Greek Cup phase two, competing for two quarterfinals spots with phase one winners. All sixteen teams from the second-tier level Greek A2 Basket League's 2020–21 season will start from phase one, competing for one spot in phase two of the cup. All rounds were played under a single elimination format.