| 2021-09-19 | MjondalenvSandefjordEliteserien · Norway | 1–1 | Eliteserien · Norway |
| 2021-09-19 | Austin FCvSan Jose EarthquakesMLS · United States | 3–4 | MLS · United States |
| 2021-09-19 | ClermontvBrestLigue 1 · France | 1–1 | Ligue 1 · France |
| 2021-09-19 | LamiavOlympiakosSuper League · Greece | 1–2 | Super League · Greece |
| 2021-09-19 | AntwerpvSeraingPro League · Belgium | 2–1 | Pro League · Belgium |
| 2021-09-19 | Erzgebirge AuevPaderborn2. Bundesliga · Germany | 1–4 | 2. Bundesliga · Germany |
| 2021-09-19 | EmpolivSampdoriaSerie A · Italy | 0–3 | Serie A · Italy |
| 2021-09-19 | Toronto FCvNashville SCMLS · United States | 2–1 | MLS · United States |
| 2021-09-19 | BrightonvLeicesterPremier League · England | 2–1 | Premier League · England |
| 2021-09-19 | PSV EindhovenvFeyenoordEredivisie · Netherlands | 0–4 | Eredivisie · Netherlands |
| 2021-09-19 | SalzburgvSK RapidBundesliga · Austria | 2–0 | Bundesliga · Austria |
| 2021-09-19 | Houston DynamovFC DallasMLS · United States | 3–2 | MLS · United States |
| 2021-09-19 | Randers FCvNordsjaellandSuperliga · Denmark | 3–2 | Superliga · Denmark |
| 2021-09-19 | West HamvMan UnitedPremier League · England | 1–2 | Premier League · England |
| 2021-09-19 | CorinthiansvAmerica MGSerie A · Brazil | 1–1 | Serie A · Brazil |
| 2021-09-19 | Sepsi Sf. GheorghevUTA AradSuperliga · Romania | 0–0 | Superliga · Romania |
| 2021-09-19 | Go Ahead EaglesvZwolleEredivisie · Netherlands | 1–0 | Eredivisie · Netherlands |
| 2021-09-19 | ParmavCremoneseSerie B · Italy | 1–2 | Serie B · Italy |
| 2021-09-19 | VeronavRomaSerie A · Italy | 3–2 | Serie A · Italy |
| 2021-09-19 | VizelavPacos FerreiraPrimeira Liga · Portugal | 1–1 | Primeira Liga · Portugal |
| 2021-09-19 | AngersvNantesLigue 1 · France | 1–4 | Ligue 1 · France |
| 2021-09-19 | LegiavLecznaEkstraklasa · Poland | 3–1 | Ekstraklasa · Poland |
| 2021-09-19 | Nicev MonacoLigue 1 · France | 2–2 | Ligue 1 · France |
| 2021-09-19 | Pari NNvArsenal TulaPremier League · Russia | 2–3 | Premier League · Russia |
| 2021-09-19 | PatronatovEstudiantes L.P.Liga Profesional · Argentina | 1–2 | Liga Profesional · Argentina |
| 2021-09-19 | LivingstonvCelticPremiership · Scotland | 1–0 | Premiership · Scotland |
| 2021-09-19 | Gornik Z.vWarta PoznanEkstraklasa · Poland | 1–0 | Ekstraklasa · Poland |
| 2021-09-19 | ReimsvLorientLigue 1 · France | 0–0 | Ligue 1 · France |
| 2021-09-19 | SochivDynamo MoscowPremier League · Russia | 0–1 | Premier League · Russia |
| 2021-09-19 | PortovMoreirensePrimeira Liga · Portugal | 5–0 | Primeira Liga · Portugal |
| 2021-09-19 | OstersundsvElfsborgAllsvenskan · Sweden | 3–1 | Allsvenskan · Sweden |
| 2021-09-19 | TolucavClub AmericaLiga MX · Mexico | 3–1 | Liga MX · Mexico |
| 2021-09-19 | HonkavHJKVeikkausliiga · Finland | 0–0 | Veikkausliiga · Finland |
| 2021-09-19 | PonferradinavMalagaLa Liga 2 · Spain | 4–0 | La Liga 2 · Spain |
| 2021-09-19 | Asteras TripolisvPAOKSuper League · Greece | 0–1 | Super League · Greece |
| 2021-09-19 | StuttgartvLeverkusenBundesliga · Germany | 1–3 | Bundesliga · Germany |
| 2021-09-19 | EibarvSp GijonLa Liga 2 · Spain | 3–2 | La Liga 2 · Spain |
| 2021-09-19 | DarmstadtvDresden2. Bundesliga · Germany | 1–0 | 2. Bundesliga · Germany |
| 2021-09-19 | MallorcavVillarrealLa Liga · Spain | 0–0 | La Liga · Spain |
| 2021-09-19 | Mazatlan FCvUNAM PumasLiga MX · Mexico | 2–2 | Liga MX · Mexico |
| 2021-09-19 | NorrkopingvOrebroAllsvenskan · Sweden | 3–0 | Allsvenskan · Sweden |
| 2021-09-19 | HuracanvIndependienteLiga Profesional · Argentina | 0–1 | Liga Profesional · Argentina |
| 2021-09-19 | GiresunsporvKonyasporSüper Lig · Turkey | 0–0 | Süper Lig · Turkey |
| 2021-09-19 | Sarpsborg 08vRosenborgEliteserien · Norway | 1–3 | Eliteserien · Norway |
| 2021-09-19 | A. KlagenfurtvLASKBundesliga · Austria | 1–1 | Bundesliga · Austria |
| 2021-09-19 | Philadelphia UnionvOrlando CityMLS · United States | 3–1 | MLS · United States |
| 2021-09-19 | Sao PaulovAtletico GOSerie A · Brazil | 2–1 | Serie A · Brazil |
| 2021-09-19 | StandardvAnderlechtPro League · Belgium | 0–1 | Pro League · Belgium |
| 2021-09-19 | BetisvEspanolLa Liga · Spain | 2–2 | La Liga · Spain |
| 2021-09-19 | Colon Santa FEvCentral CordobaLiga Profesional · Argentina | 1–0 | Liga Profesional · Argentina |