| 1 | Sun Sep 7 | vs Panthers | W26-10 | 1-0 | 1.000 | TIAA Bank Field · Jacksonville, FL |
| 2 | Sun Sep 14 | atBengals | L27-31 | 1-1 | .500 | Paycor Stadium · Cincinnati, OH |
| 3 | Sun Sep 21 | vsTexans | W17-10 | 2-1 | .667 | TIAA Bank Field · Jacksonville, FL |
| 4 | Sun Sep 28 | at49ers | W26-21 | 3-1 | .750 | Levi's® Stadium · Santa Clara, CA |
| 5 | Mon Oct 6 | vsChiefs | W31-28 | 4-1 | .800 | TIAA Bank Field · Jacksonville, FL |
| 6 | Sun Oct 12 | vsSeahawks | L12-20 | 4-2 | .667 | TIAA Bank Field · Jacksonville, FL |
| 7 | Sun Oct 19 | vsRams | L7-35 | 4-3 | .571 | Wembley Stadium · London, England |
| --bye week-- |
| 9 | Sun Nov 2 | atRaiders | W30-29 (OT) | 5-3 | .625 | Allegiant Stadium · Las Vegas, NV |
| 10 | Sun Nov 9 | atTexans | L29-36 | 5-4 | .556 | NRG Stadium · Houston, TX |
| 11 | Sun Nov 16 | vsChargers | W35-6 | 6-4 | .600 | TIAA Bank Field · Jacksonville, FL |
| 12 | Sun Nov 23 | atCardinals | W27-24 (OT) | 7-4 | .636 | State Farm Stadium · Glendale, AZ |
| 13 | Sun Nov 30 | atTitans | W25-3 | 8-4 | .667 | Nissan Stadium · Nashville, TN |
| 14 | Sun Dec 7 | vsColts | W36-19 | 9-4 | .692 | TIAA Bank Field · Jacksonville, FL |
| 15 | Sun Dec 14 | vsJets | W48-20 | 10-4 | .714 | TIAA Bank Field · Jacksonville, FL |
| 16 | Sun Dec 21 | atBroncos | W34-20 | 11-4 | .733 | Empower Field at Mile High · Denver, CO |
| 17 | Sun Dec 28 | atColts | W23-17 | 12-4 | .750 | Lucas Oil Stadium · Indianapolis, IN |
| 18 | Sun Jan 4 | vsTitans | W41-7 | 13-4 | .765 | TIAA Bank Field · Jacksonville, FL |
| WC | Sun Jan 11 | vsBills | L24-27 | 13-4 | .765 | TIAA Bank Field · Jacksonville, FL |
