| 18 Apr 21 | r02        | Columbus CrewColumbus Crew | 0 - 0 | Philadelphia UnionPhiladelphia |
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| 25 Apr 21 | r03        | Philadelphia UnionPhiladelphia | 1 - 2 | Inter MiamiInter Miami |
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| 02 May 21 | r04        | Philadelphia UnionPhiladelphia | 0 - 2 | New York CityNew York City |
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| 08 May 21 | r05        | Chicago FireChicago Fire | 0 - 2 | Philadelphia UnionPhiladelphia |
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| 14 May 21 | r06        | Philadelphia UnionPhiladelphia | 1 - 1 | New England Rev.New England R |
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| 17 May 21 | r07        | Philadelphia UnionPhiladelphia | 1 - 0 | New York Red BullsNew York Red |
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| 25 May 21 | r09        | DC UnitedDC United | 0 - 1 | Philadelphia UnionPhiladelphia |
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| 31 May 21 | r10        | Philadelphia UnionPhiladelphia | 3 - 0 | Portland TimbersPortland Timb |
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| 20 Jun 21 | r12        | Atlanta UnitedAtlanta Unite | 2 - 2 | Philadelphia UnionPhiladelphia |
| 24 Jun 21 | r12        | Philadelphia UnionPhiladelphia | 1 - 0 | Columbus CrewColumbus Crew |
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| 27 Jun 21 | r13        | Chicago FireChicago Fire | 3 - 3 | Philadelphia UnionPhiladelphia |
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| 04 Jul 21 | r15        | Nashville SCNashville SC | 1 - 0 | Philadelphia UnionPhiladelphia |
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| 09 Jul 21 | r16        | New York Red BullsNew York Red | 1 - 1 | Philadelphia UnionPhiladelphia |
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| 18 Jul 21 | r17        | Philadelphia UnionPhiladelphia | 2 - 1 | DC UnitedDC United |
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| 23 Jul 21 | r19        | Orlando CityOrlando City | 2 - 1 | Philadelphia UnionPhiladelphia |
| 26 Jul 21 | r19        | Inter MiamiInter Miami | 1 - 1 | Philadelphia UnionPhiladelphia |
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| 01 Aug 21 | r22        | Philadelphia UnionPhiladelphia | 1 - 1 | Chicago FireChicago Fire |
| 05 Aug 21 | r22        | Philadelphia UnionPhiladelphia | 3 - 0 | Toronto FCToronto FC |
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| 08 Aug 21 | r24        | New England Rev.New England R | 2 - 1 | Philadelphia UnionPhiladelphia |
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| 19 Aug 21 | r26        | Philadelphia UnionPhiladelphia | 1 - 0 | New York CityNew York City |
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| 22 Aug 21 | r27        | Philadelphia UnionPhiladelphia | 1 - 1 | CF MontréalCF Montréal |
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| 29 Aug 21 | r29        | DC UnitedDC United | 3 - 1 | Philadelphia UnionPhiladelphia |
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| 04 Sep 21 | r32        | Philadelphia UnionPhiladelphia | 0 - 1 | New England Rev.New England R |
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| 19 Sep 21 | r34        | Philadelphia UnionPhiladelphia | 3 - 1 | Orlando CityOrlando City |
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| 25 Sep 21 | r35        | Philadelphia UnionPhiladelphia | 1 - 0 | Atlanta UnitedAtlanta Unite |
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| 29 Sep 21 | r36        | New York Red BullsNew York Red | 1 - 1 | Philadelphia UnionPhiladelphia |
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| 03 Oct 21 | r38        | Philadelphia UnionPhiladelphia | 3 - 0 | Columbus CrewColumbus Crew |
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| 10 Oct 21 | r25        | FC CincinnatiFC Cincinnati | 1 - 2 | Philadelphia UnionPhiladelphia |
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| 16 Oct 21 | r38        | CF MontréalCF Montréal | 2 - 2 | Philadelphia UnionPhiladelphia |
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| 21 Oct 21 | r40        | Minnesota UnitedMinnesota Uni | 3 - 2 | Philadelphia UnionPhiladelphia |
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| 24 Oct 21 | r42        | Philadelphia UnionPhiladelphia | 1 - 0 | Nashville SCNashville SC |
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| 28 Oct 21 | r43        | Toronto FCToronto FC | 2 - 2 | Philadelphia UnionPhiladelphia |
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| 31 Oct 21 | r44        | Philadelphia UnionPhiladelphia | 2 - 0 | FC CincinnatiFC Cincinnati |
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| 07 Nov 21 | r46        | New York CityNew York City | 1 - 1 | Philadelphia UnionPhiladelphia |
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| 20 Nov 21 | Playoff        | Philadelphia UnionPhiladelphia | 1 - 0 | New York Red BullsNew York Red |
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| 28 Nov 21 | QF        | Philadelphia UnionPhiladelphia | 1 - 1 | Nashville SCNashville SC |
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| 05 Dec 21 | SF        | Philadelphia UnionPhiladelphia | 1 - 2 | New York CityNew York City |