| 2. Round | 07/04/2022 | Louisville City FC | - | Chattanooga Red Wolves | 1:0 |  |
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| 3. Round | 21/04/2022 | Louisville City FC | - | St. Louis City SC 2 | 9:8 pso | ||||
| 4. Round | 11/05/2022 | Detroit City FC | - | Louisville City FC | 2:4 pso | |
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| Round of 16 | 26/05/2022 | Louisville City FC | - | Nashville SC | 1:2 |
USA