| 1. Round | 18/04/2021 | Chicago Fire | - | New England Revolution | 2:2 | ||||
| 1. Round | 25/04/2021 | Atlanta United FC | - | Chicago Fire | 3:1 | ||||
| 2. Round | 01/05/2021 | New York RB | - | Chicago Fire | 2:0 |  |
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| 2. Round | 08/05/2021 | Chicago Fire | - | Philadelphia Union | 0:2 | ||||
| 2. Round | 14/05/2021 | D.C. United | - | Chicago Fire | 1:0 | ||||
| 2. Round | 22/05/2021 | Chicago Fire | - | Inter Miami CF | 1:0 | ||||
| 2. Round | 29/05/2021 | Chicago Fire | - | CF Montréal | 0:1 | ||||
| 3. Round | 20/06/2021 | Columbus Crew | - | Chicago Fire | 2:0 | ||||
| 3. Round | 24/06/2021 | Chicago Fire | - | FC Cincinnati | 0:1 | ||||
| 3. Round | 27/06/2021 | Chicago Fire | - | Philadelphia Union | 3:3 | ||||
| 5. Round | 01/08/2021 | Philadelphia Union | - | Chicago Fire | 1:1 | ||||
| 5. Round | 05/08/2021 | Chicago Fire | - | New York City FC | 0:0 | ||||
| 5. Round | 08/08/2021 | Chicago Fire | - | New York RB | 2:1 | ||||
| 5. Round | 15/08/2021 | Chicago Fire | - | Columbus Crew | 1:0 | ||||
| 5. Round | 19/08/2021 | Inter Miami CF | - | Chicago Fire | 3:2 |  |
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| 5. Round | 22/08/2021 | Orlando City | - | Chicago Fire | 1:0 | ||||
| 7. Round | 03/10/2021 | Toronto FC | - | Chicago Fire | 3:1 |
Costa Rica