| Rk | Day | Date | Tm | Opp | Tm | Opp | |||
|---|---|---|---|---|---|---|---|---|---|
| 1 | Sun | September 7, 1980 | L | Houston Oilers | @ | Pittsburgh Steelers | 17 | 31 | box |
| 2 | Mon | September 15, 1980 | W | Houston Oilers | @ | Cleveland Browns | 16 | 7 | box |
| 3 | Sun | September 21, 1980 | W | Houston Oilers | Baltimore Colts | 21 | 16 | box | |
| 4 | Sun | September 28, 1980 | W | Houston Oilers | @ | Cincinnati Bengals | 13 | 10 | box |
| 5 | Sun | October 5, 1980 | L | Houston Oilers | Seattle Seahawks | 7 | 26 | box | |
| 6 | Sun | October 12, 1980 | L | Houston Oilers | @ | Kansas City Chiefs | 20 | 21 | box |
| 7 | Sun | October 19, 1980 | W | Houston Oilers | Tampa Bay Buccaneers | 20 | 14 | box | |
| 8 | Sun | October 26, 1980 | W | Houston Oilers | Cincinnati Bengals | 23 | 3 | box | |
| 9 | Sun | November 2, 1980 | W | Houston Oilers | @ | Denver Broncos | 20 | 16 | box |
| 10 | Mon | November 10, 1980 | W | Houston Oilers | New England Patriots | 38 | 34 | box | |
| 11 | Sun | November 16, 1980 | W | Houston Oilers | @ | Chicago Bears | 10 | 6 | box |
| 12 | Sun | November 23, 1980 | L | Houston Oilers | @ | New York Jets | 28 | 31 | box |
| 13 | Sun | November 30, 1980 | L | Houston Oilers | Cleveland Browns | 14 | 17 | box | |
| 14 | Thu | December 4, 1980 | W | Houston Oilers | Pittsburgh Steelers | 6 | 0 | box | |
| 15 | Sun | December 14, 1980 | W | Houston Oilers | @ | Green Bay Packers | 22 | 3 | box |
| 16 | Sun | December 21, 1980 | W | Houston Oilers | Minnesota Vikings | 20 | 16 | box | |
| 17 | Sun | December 28, 1980 | L | Houston Oilers | @ | Oakland Raiders | 7 | 27 | box |