| Week 1 | Indianapolis Colts vs. Houston Texans | Sunday, September 11th, 2022 at 1:00pm ET |
| Week 2 | Indianapolis Colts vs. Jacksonville Jaguars | Sunday, September 18th, 2022 at 1:00pm ET |
| Week 3 | Kansas City Chiefs vs. Indianapolis Colts | Sunday, September 25th, 2022 at 1:00pm ET |
| Week 4 | Tennessee Titans vs. Indianapolis Colts | Sunday, October 2nd, 2022 at 1:00pm ET |
| Week 5 | Indianapolis Colts vs. Denver Broncos | Thursday, October 6th, 2022 at 8:15pm ET |
| Week 6 | Jacksonville Jaguars vs. Indianapolis Colts | Sunday, October 16th, 2022 at 1:00pm ET |
| Week 7 | Indianapolis Colts vs. Tennessee Titans | Sunday, October 23rd, 2022 at 1:00pm ET |
| Week 8 | Washington Commanders vs. Indianapolis Colts | Sunday, October 30th, 2022 at 4:25pm ET |
| Week 9 | Indianapolis Colts vs. New England Patriots | Sunday, November 6th, 2022 at 1:00pm ET |
| Week 10 | Indianapolis Colts vs. Las Vegas Raiders | Sunday, November 13th, 2022 at 4:05pm ET |
| Week 11 | Philadelphia Eagles vs. Indianapolis Colts | Sunday, November 20th, 2022 at 1:00pm ET |
| Week 12 | Pittsburgh Steelers vs. Indianapolis Colts | Monday, November 28th, 2022 at 8:15pm ET |
| Week 13 | Indianapolis Colts vs. Dallas Cowboys | Sunday, December 4th, 2022 at 8:20pm ET |
| Week 14 | Bye Week | |
| Week 15 | Indianapolis Colts vs. Minnesota Vikings | Saturday, December 17th, 2022 at 1:00pm ET |
| Week 16 | Los Angeles Chargers vs. Indianapolis Colts | Monday, December 26th, 2022 at 8:15pm ET |
| Week 17 | Indianapolis Colts vs. New York Giants | Sunday, January 1st, 2023 at 1:00pm ET |
| Week 18 | Houston Texans vs. Indianapolis Colts | Sunday, January 8th, 2023 at 1:00pm ET |
