| Week 1 | Miami Dolphins vs. Indianapolis Colts | Sunday, September 7th, 2025 at 1:00pm ET |
| Week 2 | Denver Broncos vs. Indianapolis Colts | Sunday, September 14th, 2025 at 4:05pm ET |
| Week 3 | Indianapolis Colts vs. Tennessee Titans | Sunday, September 21st, 2025 at 1:00pm ET |
| Week 4 | Indianapolis Colts vs. Los Angeles Rams | Sunday, September 28th, 2025 at 4:05pm ET |
| Week 5 | Las Vegas Raiders vs. Indianapolis Colts | Sunday, October 5th, 2025 at 1:00pm ET |
| Week 6 | Arizona Cardinals vs. Indianapolis Colts | Sunday, October 12th, 2025 at 1:00pm ET |
| Week 7 | Indianapolis Colts vs. Los Angeles Chargers | Sunday, October 19th, 2025 at 4:05pm ET |
| Week 8 | Tennessee Titans vs. Indianapolis Colts | Sunday, October 26th, 2025 at 4:25pm ET |
| Week 9 | Indianapolis Colts vs. Pittsburgh Steelers | Sunday, November 2nd, 2025 at 1:00pm ET |
| Week 10 | Atlanta Falcons vs. Indianapolis Colts | Sunday, November 9th, 2025 at 9:30am ET |
| Week 11 | Bye Week | |
| Week 12 | Indianapolis Colts vs. Kansas City Chiefs | Sunday, November 23rd, 2025 at 1:00pm ET |
| Week 13 | Houston Texans vs. Indianapolis Colts | Sunday, November 30th, 2025 at 1:00pm ET |
| Week 14 | Indianapolis Colts vs. Jacksonville Jaguars | Sunday, December 7th, 2025 at 1:00pm ET |
| Week 15 | Indianapolis Colts vs. Seattle Seahawks | 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 | Jacksonville Jaguars vs. Indianapolis Colts | Sunday, December 28th, 2025 at 1:00pm ET |
| Week 18 | Indianapolis Colts vs. Houston Texans | Sunday, January 4th, 2026 at 1:00pm ET |
