| Sábado 16 de Septiembre |
| Juventus | 3 - 1 | Lazio | 08:00 |
| RB Leipzig | 3 - 0 | FC Augsburg | 08:30 |
| FC Koln | 1 - 3 | 1899 Hoffenheim | 08:30 |
| FSV Mainz 05 | 1 - 3 | VfB Stuttgart | 08:30 |
| VfL Wolfsburg | 2 - 1 | Union Berlin | 08:30 |
| SC Freiburg | 2 - 4 | Borussia Dortmund | 08:30 |
| Inter | 5 - 1 | AC Milan | 11:00 |
| VfL BOCHUM | 1 - 1 | Eintracht Frankfurt | 11:30 |
| Genoa | 2 - 2 | Napoli | 13:45 |
| Porto II | 0 - 2 | Marítimo | 05:00 |
| Wolves | 1 - 3 | Liverpool | 06:30 |
| Athletic Club | 3 - 0 | Cadiz | 07:00 |
| Red Star Zürich | 0 - 0 | Emmen | 09:00 |
| West Ham | 1 - 3 | Manchester City | 09:00 |
| Tottenham | 2 - 1 | Sheffield Utd | 09:00 |
| Manchester United | 1 - 3 | Brighton | 09:00 |
| Fulham | 1 - 0 | Luton | 09:00 |
| Aston Villa | 3 - 1 | Crystal Palace | 09:00 |
| Valencia | 3 - 0 | Atletico Madrid | 09:15 |
| Reggiana | 2 - 2 | Cremonese | 09:15 |
| Santa Clara | 0 - 0 | Penafiel | 09:30 |
| Feyenoord | 6 - 1 | Heerenveen | 09:30 |
| Rio Ave | 1 - 1 | Famalicao | 09:30 |
| Rennes | 2 - 2 | Lille | 10:00 |
| Newcastle | 1 - 0 | Brentford | 11:30 |
| Celta Vigo | 0 - 1 | Mallorca | 11:30 |
| Vitesse | 0 - 2 | Waalwijk | 11:45 |
| Farense | 3 - 1 | SC Braga | 12:00 |
| Fortuna Sittard | 3 - 1 | FC Volendam | 13:00 |
| PSV Eindhoven | 4 - 0 | NEC Nijmegen | 13:00 |
| Heracles | 1 - 3 | Utrecht | 14:00 |
| Lens | 0 - 1 | Metz | 14:00 |
| Barcelona | 5 - 0 | Real Betis | 14:00 |
| Vizela | 1 - 2 | Benfica | 14:30 |
| SV Elversberg | 2 - 1 | Hamburger SV | 06:00 |
| Arminia Bielefeld | 0 - 2 | Freiburg II | 07:00 |
| Caen | 1 - 2 | Saint Etienne | 08:00 |
| Watford | 2 - 0 | Birmingham | 09:00 |
| Norwich | 1 - 0 | Stoke City | 09:00 |
| Bristol City | 0 - 0 | West Brom | 09:00 |
| Huesca | 2 - 2 | Villarreal II | 09:15 |
| Alcorcon | 0 - 2 | Levante | 11:30 |
| Valladolid | 1 - 0 | FC Cartagena | 11:30 |
| Valenciennes | 1 - 2 | Bordeaux | 12:00 |
| Auxerre | 2 - 2 | PAU | 12:00 |
| Annecy | 0 - 0 | Estac Troyes | 12:00 |
| Rodez | 4 - 1 | Angers | 12:00 |
| FC Schalke 04 | 4 - 3 | FC Magdeburg | 13:30 |
| Necaxa | 1 - 1 | FC Juarez | 18:00 |
| Monterrey | 3 - 1 | Leon | 20:00 |
| Venados FC | 1 - 0 | Celaya | 20:05 |
| Tlaxcala | 2 - 1 | Alebrijes de Oaxaca | 22:05 |
| Club America | 4 - 0 | Guadalajara Chivas | 22:10 |
| Tacuary | 0 - 4 | Libertad | 15:30 |
| Olimpia | 3 - 1 | General Caballero | 18:00 |
| Pumas UNAM W | 5 - 1 | Toluca W | 13:00 |
| Querétaro W | 0 - 4 | Tigres UANL W | 18:06 |
| Mushuc Runa SC | 2 - 0 | Delfin SC | 13:00 |
| Guayaquil City FC | 0 - 0 | Deportivo Cuenca | 15:30 |
| El Nacional | 1 - 1 | Emelec | 18:00 |
| Vasco DA Gama | 4 - 2 | Fluminense | 14:00 |
| Atletico-MG | 1 - 0 | Botafogo | 19:00 |
| Newells Old Boys | 1 - 1 | Union Santa Fe | 13:00 |
| San Lorenzo | 1 - 1 | Racing Club | 15:00 |
| Atletico Tucuman | 1 - 0 | Barracas Central | 17:00 |
| Talleres Cordoba | 0 - 0 | Instituto Cordoba | 19:00 |
| Deportivo Municipal | 0 - 3 | Cesar Vallejo | 13:00 |
| Deportivo Garcilaso | 2 - 1 | Cusco | 16:00 |
| Sporting Cristal | 0 - 0 | Universitario | 20:30 |
| America de Cali | 5 - 0 | Chico | 20:15 |
| New York City FC | 0 - 0 | New York Red Bulls | 14:30 |
| Atlanta United FC | 5 - 2 | Inter Miami | 16:00 |
| Orlando City SC | 4 - 3 | Columbus Crew | 18:30 |
| Montreal Impact | 0 - 0 | Chicago Fire | 18:30 |
| Charlotte | 0 - 0 | DC United | 18:30 |
| Toronto FC | 1 - 2 | Vancouver Whitecaps | 18:30 |
| Philadelphia Union | 2 - 2 | FC Cincinnati | 18:30 |
| Houston Dynamo | 1 - 1 | St. Louis City | 19:30 |
| Minnesota Stars FC | 0 - 1 | Sporting Kansas City | 19:30 |
| FC Dallas | 1 - 1 | Seattle Sounders | 19:30 |
| Colorado Rapids | 2 - 1 | New England Revolution | 20:30 |
| San Jose Earthquakes | 2 - 1 | Real Salt Lake | 21:30 |
| Los Angeles FC | 4 - 2 | Los Angeles Galaxy | 21:30 |
| Deportivo Madryn | 4 - 0 | Villa Dalmine | 13:30 |
| CA Estudiantes | 0 - 0 | Independ. Rivadavia | 19:00 |
| Defensores Unidos | 2 - 1 | Guillermo Brown | 13:30 |
| Flandria | 1 - 0 | Almagro | 13:30 |
| Club Atlético Güemes | 1 - 0 | Nueva Chicago | 13:30 |
| Gimnasia M. | 1 - 1 | Temperley | 14:00 |
| Almirante Brown | 0 - 2 | Estudiantes de Rio Cuarto | 15:45 |
