| 5 | Thu Oct 2 | at Rams | 8:15 PM | 3-1 | .750 | SoFi Stadium · Inglewood, CA |
| 6 | Sun Oct 12 | atBuccaneers | 4:25 PM | 3-1 | .750 | Raymond James Stadium · Tampa, FL |
| 7 | Sun Oct 19 | vsFalcons | 8:20 PM | 2-2 | .500 | Levi's® Stadium · Santa Clara, CA |
| 8 | Sun Oct 26 | atTexans | 1:00 PM | 1-3 | .250 | NRG Stadium · Houston, TX |
| 9 | Sun Nov 2 | atGiants | 1:00 PM | 1-3 | .250 | MetLife Stadium · East Rutherford, NJ |
| 10 | Sun Nov 9 | vsRams | 4:25 PM | 3-1 | .750 | Levi's® Stadium · Santa Clara, CA |
| 11 | Sun Nov 16 | atCardinals | 4:05 PM | 2-2 | .500 | State Farm Stadium · Glendale, AZ |
| 12 | Mon Nov 24 | vsPanthers | 8:15 PM | 1-3 | .250 | Levi's® Stadium · Santa Clara, CA |
| 13 | Sun Nov 30 | atBrowns | 1:00 PM | 1-3 | .250 | FirstEnergy Stadium · Cleveland, OH |
| --bye week-- |
| 15 | Sun Dec 14 | vsTitans | 4:25 PM | 0-4 | .000 | Levi's® Stadium · Santa Clara, CA |
| 16 | Mon Dec 22 | atColts | 8:15 PM | 3-1 | .750 | Lucas Oil Stadium · Indianapolis, IN |
| 17 | Sun Dec 28 | vsBears | 8:20 PM | 2-2 | .500 | Levi's® Stadium · Santa Clara, CA |
| 18 | TBD | vsSeahawks | TBD | 3-1 | .750 | Levi's® Stadium · Santa Clara, CA |
