September 22, 2021
Go Ahead Eagles 17:45 PSV Eindhoven
NEC 17:45 Utrecht
Groningen 19:00 Vitesse
Feyenoord 20:00 Heerenveen
PEC Zwolle 20:00 Sparta Rotterdam
September 23, 2021
Cambuur 17:45 Heracles Almelo
Twente 20:00 AZ
September 25, 2021
Willem II 15:30 PSV Eindhoven
Ajax 17:45 Groningen
Vitesse 17:45 Fortuna Sittard
Feyenoord 20:00 NEC
Utrecht 20:00 PEC Zwolle
September 26, 2021
Sparta Rotterdam 11:15 Cambuur
AZ 13:30 Go Ahead Eagles
Heerenveen 13:30 Twente
Heracles Almelo 15:45 RKC Waalwijk
October 1, 2021
Groningen 19:00 Twente