| 2021-10-16 | HibernianvDundee UnitedPremiership · Scotland | 0–3 | Premiership · Scotland |
| 2021-10-16 | CowdenbeathvStenhousemuirLeague Two · Scotland | 0–2 | League Two · Scotland |
| 2021-10-16 | PerugiavBresciaSerie B · Italy | 1–0 | Serie B · Italy |
| 2021-10-16 | Columbus CrewvInter MiamiMLS · United States | 4–0 | MLS · United States |
| 2021-10-16 | SociedadvMallorcaLa Liga · Spain | 1–0 | La Liga · Spain |
| 2021-10-16 | RotherhamvPortsmouthLeague One · England | 4–1 | League One · England |
| 2021-10-16 | St. GilloisevSeraingPro League · Belgium | 4–2 | Pro League · Belgium |
| 2021-10-16 | M'gladbachvStuttgartBundesliga · Germany | 1–1 | Bundesliga · Germany |
| 2021-10-16 | PSV EindhovenvZwolleEredivisie · Netherlands | 3–1 | Eredivisie · Netherlands |
| 2021-10-16 | East FifevCove RangersLeague One · Scotland | 4–2 | League One · Scotland |
| 2021-10-16 | SochivFK RostovPremier League · Russia | 3–2 | Premier League · Russia |
| 2021-10-16 | Gimnasia L.P.vNewells Old BoysLiga Profesional · Argentina | 1–0 | Liga Profesional · Argentina |
| 2021-10-16 | AFC WimbledonvSheffield WedsLeague One · England | 2–2 | League One · England |
| 2021-10-16 | Urawa RedsvGamba OsakaJ1 League · Japan | 1–1 | J1 League · Japan |
| 2021-10-16 | Sheffield UnitedvStokeChampionship · England | 2–1 | Championship · England |
| 2021-10-16 | Las PalmasvTenerifeLa Liga 2 · Spain | 2–1 | La Liga 2 · Spain |
| 2021-10-16 | Pau FCvParis FCLigue 2 · France | 1–0 | Ligue 2 · France |
| 2021-10-16 | HuddersfieldvHullChampionship · England | 2–0 | Championship · England |
| 2021-10-16 | AlloavPeterheadLeague One · Scotland | 2–4 | League One · Scotland |
| 2021-10-16 | ApollonvAsteras TripolisSuper League · Greece | 0–1 | Super League · Greece |
| 2021-10-16 | Man CityvBurnleyPremier League · England | 2–0 | Premier League · England |
| 2021-10-16 | MiddlesbroughvPeterboroChampionship · England | 2–0 | Championship · England |
| 2021-10-16 | Mazatlan FCvAtlasLiga MX · Mexico | 1–0 | Liga MX · Mexico |
| 2021-10-16 | FalkirkvAirdrie UtdLeague One · Scotland | 0–3 | League One · Scotland |
| 2021-10-16 | FulhamvQPRChampionship · England | 4–1 | Championship · England |
| 2021-10-16 | Sp GijonvAlcorconLa Liga 2 · Spain | 1–0 | La Liga 2 · Spain |
| 2021-10-16 | LaziovInterSerie A · Italy | 3–1 | Serie A · Italy |
| 2021-10-16 | DegerforsvHalmstadAllsvenskan · Sweden | 2–1 | Allsvenskan · Sweden |
| 2021-10-16 | ColchestervHarrogateLeague Two · England | 1–0 | League Two · England |
| 2021-10-16 | Raith RvsvArbroathChampionship · Scotland | 2–1 | Championship · Scotland |
| 2021-10-16 | BlackburnvCoventryChampionship · England | 2–2 | Championship · England |
| 2021-10-16 | RodezvSochauxLigue 2 · France | 0–1 | Ligue 2 · France |
| 2021-10-16 | AC OuluvMariehamnVeikkausliiga · Finland | 1–2 | Veikkausliiga · Finland |
| 2021-10-16 | OxfordvPlymouthLeague One · England | 1–3 | League One · England |
| 2021-10-16 | Arsenal TulavZenitPremier League · Russia | 2–1 | Premier League · Russia |
| 2021-10-16 | For SittardvCambuurEredivisie · Netherlands | 1–0 | Eredivisie · Netherlands |
| 2021-10-16 | NecaxavPueblaLiga MX · Mexico | 0–1 | Liga MX · Mexico |
| 2021-10-16 | HeerenveenvAjaxEredivisie · Netherlands | 0–2 | Eredivisie · Netherlands |
| 2021-10-16 | GiresunsporvRizesporSüper Lig · Turkey | 2–0 | Süper Lig · Turkey |
| 2021-10-16 | GironavHuescaLa Liga 2 · Spain | 1–3 | La Liga 2 · Spain |
| 2021-10-16 | Bristol CityvBournemouthChampionship · England | 0–2 | Championship · England |
| 2021-10-16 | Termalica B-B.vLechia GdanskEkstraklasa · Poland | 0–2 | Ekstraklasa · Poland |
| 2021-10-16 | NorthamptonvMansfieldLeague Two · England | 2–0 | League Two · England |
| 2021-10-16 | SwindonvRochdaleLeague Two · England | 2–2 | League Two · England |
| 2021-10-16 | BrentfordvChelseaPremier League · England | 0–1 | Premier League · England |
| 2021-10-16 | Inter TurkuvKuPSVeikkausliiga · Finland | 2–3 | Veikkausliiga · Finland |
| 2021-10-16 | SalfordvHartlepoolLeague Two · England | 2–0 | League Two · England |
| 2021-10-16 | SivassporvAntalyasporSüper Lig · Turkey | 2–2 | Süper Lig · Turkey |
| 2021-10-16 | DoncastervWycombeLeague One · England | 0–2 | League One · England |
| 2021-10-16 | PordenonevTernanaSerie B · Italy | 1–3 | Serie B · Italy |