Full Schedule
| Matchup | Week | Date/Time | Spread | Total | Result |
|---|---|---|---|---|---|
| HOUat Houston Texans | 1 | Sun, Sep 13, 12:00 PM | BUF -1.5 | 44.5 | W 36–31 |
| DETvs Detroit Lions | 2 | Thu, Sep 17, 7:15 PM | BUF -5.5 -2.5 | 54.5 +2 | W 41–31 |
| LACvs Los Angeles Chargers | 3 | Sun, Sep 27, 12:00 PM | BUF -4.5 -1.5 | 49.5 +1 | — |
| NEvs New England Patriots | 4 | Sun, Oct 4, 12:00 PM | BUF -3 | 49.5 | — |
| LARat Los Angeles Rams | 5 | Mon, Oct 12, 7:15 PM | BUF +3 | 53.5 | — |
| LVat Las Vegas Raiders | 6 | Sun, Oct 18, 3:25 PM | BUF -6.5 | 47.5 | — |
| BALvs Baltimore Ravens | 8 | Sun, Nov 1, 12:00 PM | BUF -2.5 | 51.5 | — |
| MINat Minnesota Vikings | 9 | Mon, Nov 9, 7:15 PM | BUF -3 | 48.5 | — |
| NYJat New York Jets | 10 | Sun, Nov 15, 12:00 PM | BUF -7 | 46.5 | — |
| MIAvs Miami Dolphins | 11 | Sun, Nov 22, 12:00 PM | BUF -11.5 | 47.5 | — |
| KCvs Kansas City Chiefs | 12 | Thu, Nov 26, 7:20 PM | BUF -2.5 | 50.5 | — |
| NEat New England Patriots | 13 | Sun, Dec 6, 3:25 PM | BUF +1.5 | 48.5 | — |
| GBat Green Bay Packers | 14 | Sun, Dec 13, 7:20 PM | BUF +1.5 | 49.5 | — |
| CHIvs Chicago Bears | 15 | Sat, Dec 19, 7:20 PM | BUF -3.5 | 51.5 | — |
| DENat Denver Broncos | 16 | Fri, Dec 25, 3:30 PM | BUF -1.5 | 46.5 | — |
| MIAat Miami Dolphins | 17 | Sun, Jan 3, 12:00 PM | BUF -7.5 | 47.5 | — |
| NYJvs New York Jets | 18 | Sat, Jan 9, 11:00 PM | BUF -10 | 43.5 | — |
Division
The Bills play in the AFC East, which means six of their games every season come against these three clubs.