| 03 Sep 78 | r01        | Buffalo BillsBuffalo Bills | 17 - 28 | Pittsburgh SteelersPittsburgh St |
| |
| 10 Sep 78 | r02        | Buffalo BillsBuffalo Bills | 20 - 21 | New York JetsNew York Jets |
| |
| 17 Sep 78 | r03        | Miami DolphinsMiami Dolphin | 31 - 24 | Buffalo BillsBuffalo Bills |
| |
| 24 Sep 78 | r04        | Buffalo BillsBuffalo Bills | 24 - 17 | Indianapolis ColtsIndianapolis |
| |
| 01 Oct 78 | r05        | Buffalo BillsBuffalo Bills | 28 - 13 | Kansas City ChiefsKansas City C |
| |
| 08 Oct 78 | r06        | New York JetsNew York Jets | 45 - 14 | Buffalo BillsBuffalo Bills |
| |
| 15 Oct 78 | r07        | Tennessee TitansTennessee Tit | 17 - 10 | Buffalo BillsBuffalo Bills |
| |
| 22 Oct 78 | r08        | Buffalo BillsBuffalo Bills | 5 - 0 | Cincinnati BengalsCincinnati Be |
| |
| 29 Oct 78 | r09        | Cleveland BrownsCleveland Bro | 41 - 20 | Buffalo BillsBuffalo Bills |
| |
| 05 Nov 78 | r10        | Buffalo BillsBuffalo Bills | 10 - 14 | New England PatriotsNew England P |
| 12 Nov 78 | r10        | Buffalo BillsBuffalo Bills | 24 - 25 | Miami DolphinsMiami Dolphin |
| |
| 19 Nov 78 | r12        | Tampa Bay BuccaneersTampa Bay Buc | 31 - 10 | Buffalo BillsBuffalo Bills |
| |
| 26 Nov 78 | r13        | Buffalo BillsBuffalo Bills | 41 - 17 | New York GiantsNew York Gian |
| |
| 03 Dec 78 | r14        | Kansas City ChiefsKansas City C | 14 - 10 | Buffalo BillsBuffalo Bills |
| |
| 10 Dec 78 | r15        | New England PatriotsNew England P | 26 - 24 | Buffalo BillsBuffalo Bills |
| |
| 17 Dec 78 | r16        | Indianapolis ColtsIndianapolis | 14 - 21 | Buffalo BillsBuffalo Bills |