| 07 Sep 80 | r01        | Buffalo BillsBuffalo Bills | 17 - 7 | Miami DolphinsMiami Dolphin |
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| 14 Sep 80 | r02        | Buffalo BillsBuffalo Bills | 20 - 10 | New York JetsNew York Jets |
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| 21 Sep 80 | r03        | New Orleans SaintsNew Orleans S | 26 - 35 | Buffalo BillsBuffalo Bills |
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| 28 Sep 80 | r04        | Buffalo BillsBuffalo Bills | 24 - 7 | Las Vegas RaidersLas Vegas Rai |
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| 05 Oct 80 | r05        | Los Angeles ChargersLos Angeles C | 24 - 26 | Buffalo BillsBuffalo Bills |
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| 12 Oct 80 | r06        | Buffalo BillsBuffalo Bills | 12 - 17 | Indianapolis ColtsIndianapolis |
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| 19 Oct 80 | r07        | Miami DolphinsMiami Dolphin | 17 - 14 | Buffalo BillsBuffalo Bills |
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| 26 Oct 80 | r08        | Buffalo BillsBuffalo Bills | 31 - 13 | New England PatriotsNew England P |
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| 02 Nov 80 | r09        | Buffalo BillsBuffalo Bills | 14 - 30 | Atlanta FalconsAtlanta Falco |
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| 09 Nov 80 | r10        | New York JetsNew York Jets | 24 - 31 | Buffalo BillsBuffalo Bills |
| 16 Nov 80 | r10        | Cincinnati BengalsCincinnati Be | 0 - 14 | Buffalo BillsBuffalo Bills |
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| 23 Nov 80 | r12        | Buffalo BillsBuffalo Bills | 28 - 13 | Pittsburgh SteelersPittsburgh St |
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| 30 Nov 80 | r13        | Indianapolis ColtsIndianapolis | 28 - 24 | Buffalo BillsBuffalo Bills |
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| 07 Dec 80 | r14        | Buffalo BillsBuffalo Bills | 10 - 7 | Los Angeles RamsLos Angeles R |
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| 14 Dec 80 | r15        | New England PatriotsNew England P | 24 - 2 | Buffalo BillsBuffalo Bills |
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| 21 Dec 80 | r16        | San Francisco 49ersSan Francisco | 13 - 18 | Buffalo BillsBuffalo Bills |
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| 03 Jan 81 | QF        | Los Angeles ChargersLos Angeles C | 20 - 14 | Buffalo BillsBuffalo Bills |