| Week 1 | San Francisco 49ers vs. Seattle Seahawks | Sunday, September 7th, 2025 at 4:05pm ET |
| Week 2 | San Francisco 49ers vs. New Orleans Saints | Sunday, September 14th, 2025 at 1:00pm ET |
| Week 3 | Arizona Cardinals vs. San Francisco 49ers | Sunday, September 21st, 2025 at 4:25pm ET |
| Week 4 | Jacksonville Jaguars vs. San Francisco 49ers | Sunday, September 28th, 2025 at 4:05pm ET |
| Week 5 | San Francisco 49ers vs. Los Angeles Rams | Thursday, October 2nd, 2025 at 8:15pm ET |
| Week 6 | San Francisco 49ers vs. Tampa Bay Buccaneers | Sunday, October 12th, 2025 at 4:25pm ET |
| Week 7 | Atlanta Falcons vs. San Francisco 49ers | Sunday, October 19th, 2025 at 8:20pm ET |
| Week 8 | San Francisco 49ers vs. Houston Texans | Sunday, October 26th, 2025 at 1:00pm ET |
| Week 9 | San Francisco 49ers vs. New York Giants | Sunday, November 2nd, 2025 at 1:00pm ET |
| Week 10 | Los Angeles Rams vs. San Francisco 49ers | Sunday, November 9th, 2025 at 4:25pm ET |
| Week 11 | San Francisco 49ers vs. Arizona Cardinals | Sunday, November 16th, 2025 at 4:05pm ET |
| Week 12 | Carolina Panthers vs. San Francisco 49ers | Monday, November 24th, 2025 at 8:15pm ET |
| Week 13 | San Francisco 49ers vs. Cleveland Browns | Sunday, November 30th, 2025 at 1:00pm ET |
| Week 14 | Bye Week | |
| Week 15 | Tennessee Titans vs. San Francisco 49ers | Sunday, December 14th, 2025 at 4:25pm ET |
| Week 16 | San Francisco 49ers vs. Indianapolis Colts | Monday, December 22nd, 2025 at 8:15pm ET |
| Week 17 | Chicago Bears vs. San Francisco 49ers | Sunday, December 28th, 2025 at 8:20pm ET |
| Week 18 | Seattle Seahawks vs. San Francisco 49ers | Sunday, January 4th, 2026 at 1:00pm ET |
