| Rk | Day | Date | Tm | Opp | Tm | Opp | |||
|---|---|---|---|---|---|---|---|---|---|
| 1 | Sun | September 7, 1980 | W | Buffalo Bills | Miami Dolphins | 17 | 7 | box | |
| 2 | Sun | September 14, 1980 | W | Buffalo Bills | New York Jets | 20 | 10 | box | |
| 3 | Sun | September 21, 1980 | W | Buffalo Bills | @ | New Orleans Saints | 35 | 26 | box |
| 4 | Sun | September 28, 1980 | W | Buffalo Bills | Oakland Raiders | 24 | 7 | box | |
| 5 | Sun | October 5, 1980 | W | Buffalo Bills | @ | San Diego Chargers | 26 | 24 | box |
| 6 | Sun | October 12, 1980 | L | Buffalo Bills | Baltimore Colts | 12 | 17 | box | |
| 7 | Sun | October 19, 1980 | L | Buffalo Bills | @ | Miami Dolphins | 14 | 17 | box |
| 8 | Sun | October 26, 1980 | W | Buffalo Bills | New England Patriots | 31 | 13 | box | |
| 9 | Sun | November 2, 1980 | L | Buffalo Bills | Atlanta Falcons | 14 | 30 | box | |
| 10 | Sun | November 9, 1980 | W | Buffalo Bills | @ | New York Jets | 31 | 24 | box |
| 11 | Sun | November 16, 1980 | W | Buffalo Bills | @ | Cincinnati Bengals | 14 | 0 | box |
| 12 | Sun | November 23, 1980 | W | Buffalo Bills | Pittsburgh Steelers | 28 | 13 | box | |
| 13 | Sun | November 30, 1980 | L | Buffalo Bills | @ | Baltimore Colts | 24 | 28 | box |
| 14 | Sun | December 7, 1980 | W | Buffalo Bills | Los Angeles Rams | 10 | 7 | box | |
| 15 | Sun | December 14, 1980 | L | Buffalo Bills | @ | New England Patriots | 2 | 24 | box |
| 16 | Sun | December 21, 1980 | W | Buffalo Bills | @ | San Francisco 49ers | 18 | 13 | box |
| 17 | Sat | January 3, 1981 | L | Buffalo Bills | @ | San Diego Chargers | 14 | 20 | box |