| 1 | Thu Sep 7 | at Chiefs | W21-20 | 1-0 | 1.000 | Arrowhead Stadium · Kansas City, MO |
| 2 | Sun Sep 17 | vs Seahawks | L31-37 (OT) | 1-1 | .500 | Ford Field · Detroit, MI |
| 3 | Sun Sep 24 | vs Falcons | W20-6 | 2-1 | .667 | Ford Field · Detroit, MI |
| 4 | Thu Sep 28 | at Packers | W34-20 | 3-1 | .750 | Lambeau Field · Green Bay, WI |
| 5 | Sun Oct 8 | vs Panthers | W42-24 | 4-1 | .800 | Ford Field · Detroit, MI |
| 6 | Sun Oct 15 | at Buccaneers | W20-6 | 5-1 | .833 | Raymond James Stadium · Tampa, FL |
| 7 | Sun Oct 22 | at Ravens | L6-38 | 5-2 | .714 | M&T Bank Stadium · Baltimore, MD |
| 8 | Mon Oct 30 | vs Raiders | W26-14 | 6-2 | .750 | Ford Field · Detroit, MI |
| --bye week-- |
| 10 | Sun Nov 12 | at Chargers | W41-38 | 7-2 | .778 | SoFi Stadium · Inglewood, CA |
| 11 | Sun Nov 19 | vs Bears | W31-26 | 8-2 | .800 | Ford Field · Detroit, MI |
| 12 | Thu Nov 23 | vs Packers | L22-29 | 8-3 | .727 | Ford Field · Detroit, MI |
| 13 | Sun Dec 3 | at Saints | W33-28 | 9-3 | .750 | Caesars Superdome · New Orleans, LA |
| 14 | Sun Dec 10 | at Bears | L13-28 | 9-4 | .692 | Soldier Field · Chicago, IL |
| 15 | Sat Dec 16 | vs Broncos | W42-17 | 10-4 | .714 | Ford Field · Detroit, MI |
| 16 | Sun Dec 24 | at Vikings | W30-24 | 11-4 | .733 | U.S. Bank Stadium · Minneapolis, MN |
| 17 | Sat Dec 30 | at Cowboys | L19-20 | 11-5 | .688 | AT&T Stadium · Arlington, TX |
| 18 | Sun Jan 7 | vs Vikings | W30-20 | 12-5 | .706 | Ford Field · Detroit, MI |
| WC | Sun Jan 14 | vs Rams | W24-23 | 12-5 | .706 | Ford Field · Detroit, MI |
| DIV | Sun Jan 21 | vs Buccaneers | W31-23 | 12-5 | .706 | Ford Field · Detroit, MI |
| CONF | Sun Jan 28 | at 49ers | L31-34 | 12-5 | .706 | Levi's® Stadium · Santa Clara, CA |