The 2021–22 Women's EHF Champions League knockout stage began on 26 March with the playoffs and ended on 5 June 2022 with the final at the MVM Dome in Budapest, Hungary, to decide the winners of the 2021–22 Women's EHF Champions League.[1] A total of twelve teams competed in the knockout phase.
In the playoffs, the eight teams ranked third to sixth in Groups A and B play against each other in two-legged home-and-away matches. The four winning teams advanced to the quarterfinals, where they were joined by the top-two teams of Groups A and B for another round of two-legged home-and-away matches. The four quarterfinal winners qualified for the final four tournament at the MVM Dome in Budapest, Hungary.
The top six teams from Groups A and B qualified for the knockout stage.
| Group | Qualified for quarterfinals | Qualified for playoffs | |||||
|---|---|---|---|---|---|---|---|
| First place | Second place | Third place | Fourth place | Fifth place | Sixth place | ||
| A | Team Esbjerg |  Rostov-Don |  FTC-Rail Cargo Hungaria |  Brest Bretagne Handball |  CSM București | BV Borussia 09 Dortmund | |
| B | Győri Audi ETO KC |  Vipers Kristiansand | Metz Handball | CSKA Moscow | Odense Håndbold | RK Krim Mercator | |
|}
All times are UTC+2 (matches on 26 March are UTC+1).
RK Krim Mercator won 55–52 on aggregate.----Metz Handball won 62–41 on aggregate.----Brest Bretagne Handball won 53–51 on aggregate.----
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Team Esbjerg won 53–52 on aggregate.----Győri Audi ETO KC won 56–44 on aggregate.--------Vipers Kristiansand won 65–49 on aggregate.
The final four was held at the MVM Dome in Budapest, Hungary on 4 and 5 June 2022. The draw took place on 10 May 2022.[2] [3]
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