| 1. Round | 25/04/2021 | Louisville City FC | - | Atlanta United II | 2:0 |  |
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| 5. Round | 22/08/2021 | OKC Energy FC | - | Louisville City FC | 0:0 | ||||
| 5. Round | 29/08/2021 | Birmingham Legion | - | Louisville City FC | 2:1 | ||||
| 6. Round | 04/09/2021 | Louisville City FC | - | FC Tulsa | 0:1 | ||||
| 6. Round | 19/09/2021 | Indy Eleven | - | Louisville City FC | 0:2 | ||||
| 6. Round | 26/09/2021 | Memphis 901 | - | Louisville City FC | 1:1 | ||||
| 6. Round | 30/09/2021 | Atlanta United II | - | Louisville City FC | 1:1 | ||||
| 7. Round | 03/10/2021 | Louisville City FC | - | New Mexico United | 3:1 | ||||
| 7. Round | 10/10/2021 | Louisville City FC | - | Sporting Kansas City 2 | 4:3 |  |
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| 7. Round | 14/10/2021 | Memphis 901 | - | Louisville City FC | 2:1 | ||||
| 7. Round | 17/10/2021 | Indy Eleven | - | Louisville City FC | 1:0 | ||||
| 7. Round | 24/10/2021 | Louisville City FC | - | Memphis 901 | 3:1 | ||||
| 7. Round | 31/10/2021 | Birmingham Legion | - | Louisville City FC | 0:1 | |
USA