| 02 May 21 | r01        | Birmingham LegionBirmingham Le | 0 - 1 | Indy ElevenIndy Eleven |
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| 09 May 21 | r02        | Indy ElevenIndy Eleven | 0 - 2 | Tulsa RoughnecksTulsa Roughne |
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| 23 May 21 | r05        | Indy ElevenIndy Eleven | 2 - 0 | Swope Park RangersSwope Park Ra |
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| 30 May 21 | r06        | Louisville CityLouisville Ci | 1 - 2 | Indy ElevenIndy Eleven |
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| 03 Jun 21 | r08        | Indy ElevenIndy Eleven | 1 - 1 | OKC EnergyOKC Energy |
| 06 Jun 21 | r08        | Indy ElevenIndy Eleven | 1 - 2 | Memphis 901Memphis 901 |
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| 10 Jun 21 | r09        | El Paso LocomotiveEl Paso Locom | 2 - 0 | Indy ElevenIndy Eleven |
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| 16 Jun 21 | r11        | Indy ElevenIndy Eleven | 0 - 1 | Pittsburgh RiverhoundsPittsburgh Ri |
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| 20 Jun 21 | r13        | Swope Park RangersSwope Park Ra | 1 - 2 | Indy ElevenIndy Eleven |
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| 27 Jun 21 | r14        | Louisville CityLouisville Ci | 3 - 3 | Indy ElevenIndy Eleven |
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| 04 Jul 21 | r16        | Indy ElevenIndy Eleven | 0 - 1 | Birmingham LegionBirmingham Le |
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| 08 Jul 21 | r17        | Atlanta United IIAtlanta Unite | 1 - 1 | Indy ElevenIndy Eleven |
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| 18 Jul 21 | r20        | Indy ElevenIndy Eleven | 1 - 1 | Memphis 901Memphis 901 |
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| 25 Jul 21 | r22        | Indy ElevenIndy Eleven | 1 - 2 | Birmingham LegionBirmingham Le |
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| 05 Aug 21 | r25        | Tulsa RoughnecksTulsa Roughne | 0 - 2 | Indy ElevenIndy Eleven |
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| 09 Aug 21 | r26        | Atlanta United IIAtlanta Unite | 6 - 2 | Indy ElevenIndy Eleven |
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| 15 Aug 21 | r27        | Indy ElevenIndy Eleven | 2 - 1 | OKC EnergyOKC Energy |
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| 19 Aug 21 | r29        | Loudoun UnitedLoudoun Unite | 4 - 1 | Indy ElevenIndy Eleven |
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| 22 Aug 21 | r30        | Swope Park RangersSwope Park Ra | 1 - 1 | Indy ElevenIndy Eleven |
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| 29 Aug 21 | r31        | Indy ElevenIndy Eleven | 2 - 0 | Real MonarchsReal Monarchs |
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| 05 Sep 21 | r33        | Indy ElevenIndy Eleven | 0 - 1 | Atlanta United IIAtlanta Unite |
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| 09 Sep 21 | r35        | Tulsa RoughnecksTulsa Roughne | 2 - 1 | Indy ElevenIndy Eleven |
| 12 Sep 21 | r35        | Indy ElevenIndy Eleven | 1 - 0 | Swope Park RangersSwope Park Ra |
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| 19 Sep 21 | r37        | Indy ElevenIndy Eleven | 0 - 2 | Louisville CityLouisville Ci |
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| 23 Sep 21 | r38        | Memphis 901Memphis 901 | 1 - 0 | Indy ElevenIndy Eleven |
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| 26 Sep 21 | r40        | OKC EnergyOKC Energy | 2 - 0 | Indy ElevenIndy Eleven |
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| 30 Sep 21 | r18        | OKC EnergyOKC Energy | 1 - 1 | Indy ElevenIndy Eleven |
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| 03 Oct 21 | r41        | Indy ElevenIndy Eleven | 1 - 1 | Atlanta United IIAtlanta Unite |
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| 10 Oct 21 | r44        | Birmingham LegionBirmingham Le | 3 - 1 | Indy ElevenIndy Eleven |
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| 17 Oct 21 | r45        | Indy ElevenIndy Eleven | 1 - 0 | Louisville CityLouisville Ci |
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| 24 Oct 21 | r47        | Indy ElevenIndy Eleven | 1 - 1 | Tulsa RoughnecksTulsa Roughne |
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| 30 Oct 21 | r49        | Memphis 901Memphis 901 | 3 - 0 | Indy ElevenIndy Eleven |
| 31 Oct 21 | r49        | Memphis 901Memphis 901 | 3 - 0 | Indy ElevenIndy Eleven |