| 1 | Thu Sep 8 | at Rams | W31-10 | 1-0 | 1.000 | SoFi Stadium · Inglewood, CA |
| 2 | Mon Sep 19 | vsTitans | W41-7 | 2-0 | 1.000 | Highmark Stadium · Orchard Park, NY |
| 3 | Sun Sep 25 | atDolphins | L19-21 | 2-1 | .667 | Hard Rock Stadium · Miami Gardens, FL |
| 4 | Sun Oct 2 | atRavens | W23-20 | 3-1 | .750 | M&T Bank Stadium · Baltimore, MD |
| 5 | Sun Oct 9 | vsSteelers | W38-3 | 4-1 | .800 | Highmark Stadium · Orchard Park, NY |
| 6 | Sun Oct 16 | atChiefs | W24-20 | 5-1 | .833 | Arrowhead Stadium · Kansas City, MO |
| --bye week-- |
| 8 | Sun Oct 30 | vsPackers | W27-17 | 6-1 | .857 | Highmark Stadium · Orchard Park, NY |
| 9 | Sun Nov 6 | atJets | L17-20 | 6-2 | .750 | MetLife Stadium · East Rutherford, NJ |
| 10 | Sun Nov 13 | vsVikings | L30-33 (OT) | 6-3 | .667 | Highmark Stadium · Orchard Park, NY |
| 11 | Sun Nov 20 | vsBrowns | W31-23 | 7-3 | .700 | Ford Field · Detroit, MI |
| 12 | Thu Nov 24 | atLions | W28-25 | 8-3 | .727 | Ford Field · Detroit, MI |
| 13 | Thu Dec 1 | atPatriots | W24-10 | 9-3 | .750 | Gillette Stadium · Foxborough, MA |
| 14 | Sun Dec 11 | vsJets | W20-12 | 10-3 | .769 | Highmark Stadium · Orchard Park, NY |
| 15 | Sat Dec 17 | vsDolphins | W32-29 | 11-3 | .786 | Highmark Stadium · Orchard Park, NY |
| 16 | Sat Dec 24 | atBears | W35-13 | 12-3 | .800 | Soldier Field · Chicago, IL |
| 18 | Sun Jan 8 | vsPatriots | W35-23 | 13-3 | .813 | Highmark Stadium · Orchard Park, NY |
| WC | Sun Jan 15 | vsDolphins | W34-31 | 13-3 | .813 | Highmark Stadium · Orchard Park, NY |
| DIV | Sun Jan 22 | vsBengals | L10-27 | 13-3 | .813 | Highmark Stadium · Orchard Park, NY |
