The 2021–22 EHF Champions League knockout stage began on 30 March with the playoffs and ended on 19 June 2022 with the final at the Lanxess Arena in Cologne, Germany, to decide the winners of the 2021–22 EHF Champions League.
In the playoffs, the eight teams ranked third to sixth in Groups A and B played against each other in two-legged home-and-away matches.
The four quarterfinal winners qualified for the final four tournament at the Lanxess Arena in Cologne, Germany.
The top six teams from Groups A and B qualified for the knockout stage.
The final four will held at the Lanxess Arena in Cologne, Germany on 18 and 19 June 2022.