| 1 | Sun Sep 8 | at Buccaneers | W31-17 | 1-0 | 1.000 | Raymond James Stadium · Tampa, FL |
| 2 | Sun Sep 15 | at Bengals | W41-17 | 2-0 | 1.000 | Paycor Stadium · Cincinnati, OH |
| 3 | Sun Sep 22 | vs Steelers | W24-20 | 3-0 | 1.000 | Levi's® Stadium · Santa Clara, CA |
| 4 | -- BYE WEEK -- |
| 5 | Mon Oct 7 | vs Browns | W31-3 | 4-0 | 1.000 | Levi's® Stadium · Santa Clara, CA |
| 6 | Sun Oct 13 | at Rams | W20-7 | 5-0 | 1.000 | SoFi Stadium · Inglewood, CA |
| 7 | Sun Oct 20 | at Commanders | W9-0 | 6-0 | 1.000 | FedEx Field · North Englewood, MD |
| 8 | Sun Oct 27 | vs Panthers | W51-13 | 7-0 | 1.000 | Levi's® Stadium · Santa Clara, CA |
| 9 | Thu Oct 31 | at Cardinals | W28-25 | 8-0 | 1.000 | State Farm Stadium · Glendale, AZ |
| 10 | Mon Nov 11 | vs Seahawks | L24-27 (OT) | 8-1 | .889 | Levi's® Stadium · Santa Clara, CA |
| 11 | Sun Nov 17 | vsCardinals | W36-26 | 9-1 | .900 | Levi's® Stadium · Santa Clara, CA |
| 12 | Sun Nov 24 | vs Packers | W37-8 | 10-1 | .909 | Levi's® Stadium · Santa Clara, CA |
| 13 | Sun Dec 1 | at Ravens | L17-20 | 10-2 | .833 | M&T Bank Stadium · Baltimore, MD |
| 14 | Sun Dec 8 | at Saints | W48-46 | 11-2 | .846 | Caesars Superdome · New Orleans, LA |
| 15 | Sun Dec 15 | vs Falcons | L22-29 | 11-3 | .786 | Levi's® Stadium · Santa Clara, CA |
| 16 | Sat Dec 21 | vsRams | W34-31 | 12-3 | .800 | Levi's® Stadium · Santa Clara, CA |
| 17 | Sun Dec 29 | atSeahawks | W26-21 | 13-3 | .813 | Lumen Field · Seattle, WA |
| DIV | Sat Jan 11 | vs Vikings | W27-10 | 13-3 | .813 | Levi's® Stadium · Santa Clara, CA |
| CONF | Sun Jan 19 | vsPackers | W37-20 | 13-3 | .813 | Levi's® Stadium · Santa Clara, CA |
| SB | Sun Feb 2 | at Chiefs | L20-31 | 13-3 | .813 | Hard Rock Stadium · Miami Gardens, FL |
