| 1 | Sun Sep 8 | vs Cardinals | W34-28 | 1-0 | 1.000 | Highmark Stadium · Orchard Park, NY |
| 2 | Thu Sep 12 | atDolphins | W31-10 | 2-0 | 1.000 | Hard Rock Stadium · Miami Gardens, FL |
| 3 | Mon Sep 23 | vsJaguars | W47-10 | 3-0 | 1.000 | Highmark Stadium · Orchard Park, NY |
| 4 | Sun Sep 29 | atRavens | L10-35 | 3-1 | .750 | M&T Bank Stadium · Baltimore, MD |
| 5 | Sun Oct 6 | atTexans | L20-23 | 3-2 | .600 | NRG Stadium · Houston, TX |
| 6 | Mon Oct 14 | atJets | W23-20 | 4-2 | .667 | MetLife Stadium · East Rutherford, NJ |
| 7 | Sun Oct 20 | vsTitans | W34-10 | 5-2 | .714 | Highmark Stadium · Orchard Park, NY |
| 8 | Sun Oct 27 | atSeahawks | W31-10 | 6-2 | .750 | Lumen Field · Seattle, WA |
| 9 | Sun Nov 3 | vsDolphins | W30-27 | 7-2 | .778 | Highmark Stadium · Orchard Park, NY |
| 10 | Sun Nov 10 | atColts | W30-20 | 8-2 | .800 | Lucas Oil Stadium · Indianapolis, IN |
| 11 | Sun Nov 17 | vsChiefs | W30-21 | 9-2 | .818 | Highmark Stadium · Orchard Park, NY |
| --bye week-- |
| 13 | Sun Dec 1 | vs49ers | W35-10 | 10-2 | .833 | Highmark Stadium · Orchard Park, NY |
| 14 | Sun Dec 8 | atRams | L42-44 | 10-3 | .769 | SoFi Stadium · Inglewood, CA |
| 15 | Sun Dec 15 | atLions | W48-42 | 11-3 | .786 | Ford Field · Detroit, MI |
| 16 | Sun Dec 22 | vsPatriots | W24-21 | 12-3 | .800 | Highmark Stadium · Orchard Park, NY |
| 17 | Sun Dec 29 | vsJets | W40-14 | 13-3 | .813 | Highmark Stadium · Orchard Park, NY |
| 18 | Sun Jan 5 | atPatriots | L16-23 | 13-4 | .765 | Gillette Stadium · Foxborough, MA |
| WC | Sun Jan 12 | vsBroncos | W31-7 | 13-4 | .765 | Highmark Stadium · Orchard Park, NY |
| DIV | Sun Jan 19 | vsRavens | W27-25 | 13-4 | .765 | Highmark Stadium · Orchard Park, NY |
| CONF | Sun Jan 26 | atChiefs | L29-32 | 13-4 | .765 | Arrowhead Stadium · Kansas City, MO |
