| 1 | Sun Sep 11 | at Bears | L10-19 | 0-1 | .000 | Soldier Field · Chicago, IL |
| 2 | Sun Sep 18 | vs Seahawks | W27-7 | 1-1 | .500 | Levi's® Stadium · Santa Clara, CA |
| 3 | Sun Sep 25 | at Broncos | L10-11 | 1-2 | .333 | Empower Field at Mile High · Denver, CO |
| 4 | Mon Oct 3 | vs Rams | W24-9 | 2-2 | .500 | Levi's® Stadium · Santa Clara, CA |
| 5 | Sun Oct 9 | at Panthers | W37-15 | 3-2 | .600 | Bank of America Stadium · Charlotte, NC |
| 6 | Sun Oct 16 | at Falcons | L14-28 | 3-3 | .500 | Mercedes-Benz Stadium · Atlanta, GA |
| 7 | Sun Oct 23 | vs Chiefs | L23-44 | 3-4 | .429 | Levi's® Stadium · Santa Clara, CA |
| 8 | Sun Oct 30 | atRams | W31-14 | 4-4 | .500 | SoFi Stadium · Inglewood, CA |
| 9 | -- BYE WEEK -- |
| 10 | Sun Nov 13 | vs Chargers | W22-16 | 5-4 | .556 | Levi's® Stadium · Santa Clara, CA |
| 11 | Mon Nov 21 | at Cardinals | W38-10 | 6-4 | .600 | State Farm Stadium · Glendale, AZ |
| 12 | Sun Nov 27 | vs Saints | W13-0 | 7-4 | .636 | Levi's® Stadium · Santa Clara, CA |
| 13 | Sun Dec 4 | vs Dolphins | W33-17 | 8-4 | .667 | Levi's® Stadium · Santa Clara, CA |
| 14 | Sun Dec 11 | vs Buccaneers | W35-7 | 9-4 | .692 | Levi's® Stadium · Santa Clara, CA |
| 15 | Thu Dec 15 | atSeahawks | W21-13 | 10-4 | .714 | Lumen Field · Seattle, WA |
| 16 | Sat Dec 24 | vs Commanders | W37-20 | 11-4 | .733 | Levi's® Stadium · Santa Clara, CA |
| 17 | Sun Jan 1 | at Raiders | W37-34 (OT) | 12-4 | .750 | Allegiant Stadium · Las Vegas, NV |
| 18 | Sun Jan 8 | vsCardinals | W38-13 | 13-4 | .765 | Levi's® Stadium · Santa Clara, CA |
| WC | Sat Jan 14 | vsSeahawks | W41-23 | 13-4 | .765 | Levi's® Stadium · Santa Clara, CA |
| DIV | Sun Jan 22 | vs Cowboys | W19-12 | 13-4 | .765 | Levi's® Stadium · Santa Clara, CA |
| CONF | Sun Jan 29 | at Eagles | L7-31 | 13-4 | .765 | Lincoln Financial Field · Philadelphia, PA |
