| 2021-09-22 | SevillavValenciaLa Liga · Spain | 3–1 | La Liga · Spain |
| 2021-09-22 | ArisvPanathinaikosSuper League · Greece | 1–0 | Super League · Greece |
| 2021-09-22 | IlvesvMariehamnVeikkausliiga · Finland | 2–0 | Veikkausliiga · Finland |
| 2021-09-22 | LyonvTroyesLigue 1 · France | 3–1 | Ligue 1 · France |
| 2021-09-22 | AntwerpvGenkPro League · Belgium | 4–2 | Pro League · Belgium |
| 2021-09-22 | NijmegenvUtrechtEredivisie · Netherlands | 0–3 | Eredivisie · Netherlands |
| 2021-09-22 | LensvStrasbourgLigue 1 · France | 0–1 | Ligue 1 · France |
| 2021-09-22 | KTPvLahtiVeikkausliiga · Finland | 1–2 | Veikkausliiga · Finland |
| 2021-09-22 | Kashima AntlersvKawasaki FrontaleJ1 League · Japan | 1–2 | J1 League · Japan |
| 2021-09-22 | EspanolvAlavesLa Liga · Spain | 1–0 | La Liga · Spain |
| 2021-09-22 | HJKvHIFKVeikkausliiga · Finland | 0–2 | Veikkausliiga · Finland |
| 2021-09-22 | AngersvMarseilleLigue 1 · France | 0–0 | Ligue 1 · France |
| 2021-09-22 | Real MadridvMallorcaLa Liga · Spain | 6–1 | La Liga · Spain |
| 2021-09-22 | Sanfrecce HiroshimavCerezo OsakaJ1 League · Japan | 0–1 | J1 League · Japan |
| 2021-09-22 | CremonesevPerugiaSerie B · Italy | 0–3 | Serie B · Italy |
| 2021-09-22 | SiriusvNorrkopingAllsvenskan · Sweden | 2–4 | Allsvenskan · Sweden |
| 2021-09-22 | St. GallenvBaselSuper League · Switzerland | 0–2 | Super League · Switzerland |
| 2021-09-22 | GoztepvHataysporSüper Lig · Turkey | 0–2 | Süper Lig · Turkey |
| 2021-09-22 | SpeziavJuventusSerie A · Italy | 2–3 | Serie A · Italy |
| 2021-09-22 | OrebrovOstersundsAllsvenskan · Sweden | 2–0 | Allsvenskan · Sweden |
| 2021-09-22 | OFI CretevAsteras TripolisSuper League · Greece | 0–0 | Super League · Greece |
| 2021-09-22 | Inter TurkuvAC OuluVeikkausliiga · Finland | 4–0 | Veikkausliiga · Finland |
| 2021-09-22 | SalernitanavVeronaSerie A · Italy | 2–2 | Serie A · Italy |
| 2021-09-22 | OlympiakosvApollonSuper League · Greece | 4–1 | Super League · Greece |
| 2021-09-22 | ElfsborgvMalmo FFAllsvenskan · Sweden | 0–1 | Allsvenskan · Sweden |
| 2021-09-22 | ZwollevSparta RotterdamEredivisie · Netherlands | 1–1 | Eredivisie · Netherlands |
| 2021-09-22 | VillarrealvElcheLa Liga · Spain | 4–1 | La Liga · Spain |
| 2021-09-22 | KayserisporvGalatasaraySüper Lig · Turkey | 3–0 | Süper Lig · Turkey |
| 2021-09-22 | JuarezvAtl. San LuisLiga MX · Mexico | 1–0 | Liga MX · Mexico |
| 2021-09-22 |  MonacovSt EtienneLigue 1 · France | 3–1 | Ligue 1 · France |
| 2021-09-22 | MontpelliervBordeauxLigue 1 · France | 3–3 | Ligue 1 · France |
| 2021-09-22 | LausannevYoung BoysSuper League · Switzerland | 1–6 | Super League · Switzerland |
| 2021-09-22 | HonkavKuPSVeikkausliiga · Finland | 0–1 | Veikkausliiga · Finland |
| 2021-09-22 | AEKvLamiaSuper League · Greece | 1–0 | Super League · Greece |
| 2021-09-22 | Go Ahead EaglesvPSV EindhovenEredivisie · Netherlands | 1–2 | Eredivisie · Netherlands |
| 2021-09-22 | DjurgardenvDegerforsAllsvenskan · Sweden | 3–2 | Allsvenskan · Sweden |
| 2021-09-22 | FeyenoordvHeerenveenEredivisie · Netherlands | 3–1 | Eredivisie · Netherlands |
| 2021-09-22 | LorientvNiceLigue 1 · France | 1–0 | Ligue 1 · France |
| 2021-09-22 | CagliarivEmpoliSerie A · Italy | 0–2 | Serie A · Italy |
| 2021-09-22 | GroningenvVitesseEredivisie · Netherlands | 0–1 | Eredivisie · Netherlands |
| 2021-09-22 | HakavSJKVeikkausliiga · Finland | 4–0 | Veikkausliiga · Finland |
| 2021-09-22 | NantesvBrestLigue 1 · France | 3–1 | Ligue 1 · France |
| 2021-09-22 | PanetolikosvPAOKSuper League · Greece | 1–2 | Super League · Greece |
| 2021-09-22 | RennesvClermontLigue 1 · France | 6–0 | Ligue 1 · France |
| 2021-09-22 | FC TokyovNagoya GrampusJ1 League · Japan | 1–1 | J1 League · Japan |
| 2021-09-22 | MetzvParis SGLigue 1 · France | 1–2 | Ligue 1 · France |
| 2021-09-22 | MilanvVeneziaSerie A · Italy | 2–0 | Serie A · Italy |
| 2021-09-21 | Crawley TownvHarrogateLeague Two · England | 2–2 | League Two · England |
| 2021-09-21 | GillinghamvCharltonLeague One · England | 1–1 | League One · England |
| 2021-09-21 | BesiktasvAd. DemirsporSüper Lig · Turkey | 3–3 | Süper Lig · Turkey |