| 12 Sep 21 | r01        | Buffalo BillsBuffalo Bills | 16 - 23 | Pittsburgh SteelersPittsburgh St |
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| 19 Sep 21 | r02        | Miami DolphinsMiami Dolphin | 0 - 35 | Buffalo BillsBuffalo Bills |
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| 26 Sep 21 | r03        | Buffalo BillsBuffalo Bills | 43 - 21 | WashingtonWashington |
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| 03 Oct 21 | r04        | Buffalo BillsBuffalo Bills | 40 - 0 | Houston TexansHouston Texan |
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| 11 Oct 21 | r05        | Kansas City ChiefsKansas City C | 20 - 38 | Buffalo BillsBuffalo Bills |
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| 19 Oct 21 | r06        | Tennessee TitansTennessee Tit | 34 - 31 | Buffalo BillsBuffalo Bills |
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| 31 Oct 21 | r08        | Buffalo BillsBuffalo Bills | 26 - 11 | Miami DolphinsMiami Dolphin |
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| 07 Nov 21 | r09        | Jacksonville JaguarsJacksonville | 9 - 6 | Buffalo BillsBuffalo Bills |
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| 14 Nov 21 | r10        | New York JetsNew York Jets | 17 - 45 | Buffalo BillsBuffalo Bills |
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| 21 Nov 21 | r11        | Buffalo BillsBuffalo Bills | 15 - 41 | Indianapolis ColtsIndianapolis |
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| 26 Nov 21 | r12        | New Orleans SaintsNew Orleans S | 6 - 31 | Buffalo BillsBuffalo Bills |
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| 07 Dec 21 | r13        | Buffalo BillsBuffalo Bills | 10 - 14 | New England PatriotsNew England P |
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| 12 Dec 21 | r14        | Tampa Bay BuccaneersTampa Bay Buc | 33 - 27 | Buffalo BillsBuffalo Bills |
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| 19 Dec 21 | r15        | Buffalo BillsBuffalo Bills | 31 - 14 | Carolina PanthersCarolina Pant |
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| 26 Dec 21 | r16        | New England PatriotsNew England P | 21 - 33 | Buffalo BillsBuffalo Bills |
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| 02 Jan 22 | r17        | Buffalo BillsBuffalo Bills | 29 - 15 | Atlanta FalconsAtlanta Falco |
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| 09 Jan 22 | r18        | Buffalo BillsBuffalo Bills | 27 - 10 | New York JetsNew York Jets |
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| 16 Jan 22 | Playoff        | Buffalo BillsBuffalo Bills | 47 - 17 | New England PatriotsNew England P |
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| 23 Jan 22 | QF        | Kansas City ChiefsKansas City C | 42 - 36 | Buffalo BillsBuffalo Bills |