The winners earned a berth in the play-off round of the 2022–23 UEFA Europa League, and also qualified for the 2022 Turkish Super Cup.
Highest-ranked team eliminated was Siirt İl Özel İdare (124).
Lowest-ranked team qualifying for the next round was Iğdır Futbol Kulübü (130).
[9] Kastamonuspor, which did not participate in the Ziraat Turkish Cup due to the negative effects of the flood disaster in Kastamonu, did not take part in the draw, while Giresunspor, which was matched with Kastamonuspor, automatically qualified for the next round.
Biggest upset was Iğdır Futbol Kulübü (130) eliminating Eskişehirspor (42).
Lowest-ranked team qualifying for the next round was Iğdır Futbol Kulübü (130).
Biggest upset was Mardin 1969 Spor (103) eliminating Gençlerbirliği (23).
Lowest-ranked team qualifying for the next round was Mardin 1969 Spor (103).
Source:[5] 14 Süper Lig and 2 First League teams compete in this round.
Source:[5] 8 Super League teams competed in this round.
[19] The match schedules for the second leg were announced on 28 April 2022.
[20] The final match schedule and location were announced on 4 April 2022.