| 1 | Sun Sep 12 | vs Steelers | L16-23 | 0-1 | .000 | Highmark Stadium · Orchard Park, NY |
| 2 | Sun Sep 19 | atDolphins | W35-0 | 1-1 | .500 | Hard Rock Stadium · Miami Gardens, FL |
| 3 | Sun Sep 26 | vsCommanders | W43-21 | 2-1 | .667 | Highmark Stadium · Orchard Park, NY |
| 4 | Sun Oct 3 | vsTexans | W40-0 | 3-1 | .750 | Highmark Stadium · Orchard Park, NY |
| 5 | Sun Oct 10 | atChiefs | W38-20 | 4-1 | .800 | Arrowhead Stadium · Kansas City, MO |
| 6 | Mon Oct 18 | atTitans | L31-34 | 4-2 | .667 | Nissan Stadium · Nashville, TN |
| --bye week-- |
| 8 | Sun Oct 31 | vsDolphins | W26-11 | 5-2 | .714 | Highmark Stadium · Orchard Park, NY |
| 9 | Sun Nov 7 | atJaguars | L6-9 | 5-3 | .625 | TIAA Bank Field · Jacksonville, FL |
| 10 | Sun Nov 14 | atJets | W45-17 | 6-3 | .667 | MetLife Stadium · East Rutherford, NJ |
| 11 | Sun Nov 21 | vsColts | L15-41 | 6-4 | .600 | Highmark Stadium · Orchard Park, NY |
| 12 | Thu Nov 25 | atSaints | W31-6 | 7-4 | .636 | Caesars Superdome · New Orleans, LA |
| 13 | Mon Dec 6 | vsPatriots | L10-14 | 7-5 | .583 | Highmark Stadium · Orchard Park, NY |
| 14 | Sun Dec 12 | atBuccaneers | L27-33 (OT) | 7-6 | .538 | Raymond James Stadium · Tampa, FL |
| 15 | Sun Dec 19 | vsPanthers | W31-14 | 8-6 | .571 | Highmark Stadium · Orchard Park, NY |
| 16 | Sun Dec 26 | atPatriots | W33-21 | 9-6 | .600 | Gillette Stadium · Foxborough, MA |
| 17 | Sun Jan 2 | vsFalcons | W29-15 | 10-6 | .625 | Highmark Stadium · Orchard Park, NY |
| 18 | Sun Jan 9 | vsJets | W27-10 | 11-6 | .647 | Highmark Stadium · Orchard Park, NY |
| WC | Sat Jan 15 | vsPatriots | W47-17 | 11-6 | .647 | Highmark Stadium · Orchard Park, NY |
| DIV | Sun Jan 23 | atChiefs | L36-42 (OT) | 11-6 | .647 | Arrowhead Stadium · Kansas City, MO |
