| 6. Round | 05/09/2021 | Rio Grande Valley FC | - | Loudoun United | 1:1 | ||||
| 6. Round | 12/09/2021 | Colorado Springs Switchbacks | - | Rio Grande Valley FC | 1:1 |  |
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| 6. Round | 19/09/2021 | Rio Grande Valley FC | - | Colorado Springs Switchbacks | 1:2 | ||||
| 6. Round | 26/09/2021 | Rio Grande Valley FC | - | Atlanta United II | 3:2 |  |
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| 6. Round | 30/09/2021 | New Mexico United | - | Rio Grande Valley FC | 2:0 | ||||
| 7. Round | 03/10/2021 | Rio Grande Valley FC | - | Real Monarchs SLC | 3:0 | ||||
| 7. Round | 17/10/2021 | Colorado Springs Switchbacks | - | Rio Grande Valley FC | 1:0 | ||||
| 7. Round | 24/10/2021 | Rio Grande Valley FC | - | New Mexico United | 2:0 | ||||
| 7. Round | 28/10/2021 | Real Monarchs SLC | - | Rio Grande Valley FC | 1:3 | ||||
| 7. Round | 31/10/2021 | Rio Grande Valley FC | - | El Paso Locomotive | 4:1 |
Cuba