| Week 1 | Philadelphia Eagles vs. Detroit Lions | Sunday, September 11th, 2022 at 1:00pm ET |
| Week 2 | Washington Commanders vs. Detroit Lions | Sunday, September 18th, 2022 at 1:00pm ET |
| Week 3 | Detroit Lions vs. Minnesota Vikings | Sunday, September 25th, 2022 at 1:00pm ET |
| Week 4 | Seattle Seahawks vs. Detroit Lions | Sunday, October 2nd, 2022 at 1:00pm ET |
| Week 5 | Detroit Lions vs. New England Patriots | Sunday, October 9th, 2022 at 1:00pm ET |
| Week 6 | Bye Week | |
| Week 7 | Detroit Lions vs. Dallas Cowboys | Sunday, October 23rd, 2022 at 1:00pm ET |
| Week 8 | Miami Dolphins vs. Detroit Lions | Sunday, October 30th, 2022 at 1:00pm ET |
| Week 9 | Green Bay Packers vs. Detroit Lions | Sunday, November 6th, 2022 at 1:00pm ET |
| Week 10 | Detroit Lions vs. Chicago Bears | Sunday, November 13th, 2022 at 1:00pm ET |
| Week 11 | Detroit Lions vs. New York Giants | Sunday, November 20th, 2022 at 1:00pm ET |
| Week 12 | Buffalo Bills vs. Detroit Lions | Thursday, November 24th, 2022 at 12:30pm ET |
| Week 13 | Jacksonville Jaguars vs. Detroit Lions | Sunday, December 4th, 2022 at 1:00pm ET |
| Week 14 | Minnesota Vikings vs. Detroit Lions | Sunday, December 11th, 2022 at 1:00pm ET |
| Week 15 | Detroit Lions vs. New York Jets | Sunday, December 18th, 2022 at 1:00pm ET |
| Week 16 | Detroit Lions vs. Carolina Panthers | Saturday, December 24th, 2022 at 1:00pm ET |
| Week 17 | Chicago Bears vs. Detroit Lions | Sunday, January 1st, 2023 at 1:00pm ET |
| Week 18 | Detroit Lions vs. Green Bay Packers | Sunday, January 8th, 2023 at 1:00pm ET |
