| 1. Jornada | 13.01.2022 | Santos Laguna | - | UANL Tigres | 1:1 |  |
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| 2. Jornada | 16.01.2022 | Deportivo Toluca | - | Santos Laguna | 3:1 | ||||
| 3. Jornada | 24.01.2022 | Santos Laguna | - | Club Necaxa | 1:4 | ||||
| 4. Jornada | 07.02.2022 | Atlas Guadalajara | - | Santos Laguna | 2:1 | ||||
| 5. Jornada | 13.02.2022 | Santos Laguna | - | CF América | 2:3 | ||||
| 6. Jornada | 19.02.2022 | FC Juárez | - | Santos Laguna | 0:0 |  |
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| 7. Jornada | 28.02.2022 | Cruz Azul | - | Santos Laguna | 1:2 | ||||
| 8. Jornada | 03.03.2022 | Santos Laguna | - | Pumas UNAM | 3:2 | ||||
| 9. Jornada | 06.03.2022 | Deportivo Guadalajara | - | Santos Laguna | 1:0 | ||||
| 10. Jornada | 14.03.2022 | Santos Laguna | - | Club Tijuana | 4:0 | ||||
| 11. Jornada | 19.03.2022 | Puebla FC | - | Santos Laguna | 2:2 | ||||
| 12. Jornada | 04.04.2022 | Santos Laguna | - | CF Pachuca | 3:1 | |
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| 13. Jornada | 10.04.2022 | CF Monterrey | - | Santos Laguna | 1:0 | ||||
| 14. Jornada | 17.04.2022 | Santos Laguna | - | Gallos Blancos | 1:1 | |
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| 15. Jornada | 20.04.2022 | Mazatlán FC | - | Santos Laguna | 1:0 | |
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| 16. Jornada | 25.04.2022 | Santos Laguna | - | Club León | 1:1 | ||||
| 17. Jornada | 01.05.2022 | Atlético San Luis | - | Santos Laguna | 1:3 | |
Uruguay
