| Week 1 | Detroit Lions vs. Green Bay Packers | Sunday, September 7th, 2025 at 4:25pm ET |
| Week 2 | Chicago Bears vs. Detroit Lions | Sunday, September 14th, 2025 at 1:00pm ET |
| Week 3 | Detroit Lions vs. Baltimore Ravens | Monday, September 22nd, 2025 at 8:15pm ET |
| Week 4 | Cleveland Browns vs. Detroit Lions | Sunday, September 28th, 2025 at 1:00pm ET |
| Week 5 | Detroit Lions vs. Cincinnati Bengals | Sunday, October 5th, 2025 at 4:25pm ET |
| Week 6 | Detroit Lions vs. Kansas City Chiefs | Sunday, October 12th, 2025 at 8:20pm ET |
| Week 7 | Tampa Bay Buccaneers vs. Detroit Lions | Monday, October 20th, 2025 at 7:00pm ET |
| Week 8 | Bye Week | |
| Week 9 | Minnesota Vikings vs. Detroit Lions | Sunday, November 2nd, 2025 at 1:00pm ET |
| Week 10 | Detroit Lions vs. Washington Commanders | Sunday, November 9th, 2025 at 4:25pm ET |
| Week 11 | Detroit Lions vs. Philadelphia Eagles | Sunday, November 16th, 2025 at 8:20pm ET |
| Week 12 | New York Giants vs. Detroit Lions | Sunday, November 23rd, 2025 at 1:00pm ET |
| Week 13 | Green Bay Packers vs. Detroit Lions | Thursday, November 27th, 2025 at 1:00pm ET |
| Week 14 | Dallas Cowboys vs. Detroit Lions | Thursday, December 4th, 2025 at 8:15pm ET |
| Week 15 | Detroit Lions vs. Los Angeles Rams | Sunday, December 14th, 2025 at 4:25pm ET |
| Week 16 | Pittsburgh Steelers vs. Detroit Lions | Sunday, December 21st, 2025 at 4:25pm ET |
| Week 17 | Detroit Lions vs. Minnesota Vikings | Thursday, December 25th, 2025 at 4:30pm ET |
| Week 18 | Detroit Lions vs. Chicago Bears | Sunday, January 4th, 2026 at 1:00pm ET |
