| 1 | Sun Sep 8 | vs Texans | L27-29 | 0-1 | .000 | Lucas Oil Stadium · Indianapolis, IN |
| 2 | Sun Sep 15 | atPackers | L10-16 | 0-2 | .000 | Lambeau Field · Green Bay, WI |
| 3 | Sun Sep 22 | vsBears | W21-16 | 1-2 | .333 | Lucas Oil Stadium · Indianapolis, IN |
| 4 | Sun Sep 29 | vsSteelers | W27-24 | 2-2 | .500 | Lucas Oil Stadium · Indianapolis, IN |
| 5 | Sun Oct 6 | atJaguars | L34-37 | 2-3 | .400 | TIAA Bank Field · Jacksonville, FL |
| 6 | Sun Oct 13 | atTitans | W20-17 | 3-3 | .500 | Nissan Stadium · Nashville, TN |
| 7 | Sun Oct 20 | vsDolphins | W16-10 | 4-3 | .571 | Lucas Oil Stadium · Indianapolis, IN |
| 8 | Sun Oct 27 | atTexans | L20-23 | 4-4 | .500 | NRG Stadium · Houston, TX |
| 9 | Sun Nov 3 | atVikings | L13-21 | 4-5 | .444 | U.S. Bank Stadium · Minneapolis, MN |
| 10 | Sun Nov 10 | vsBills | L20-30 | 4-6 | .400 | Lucas Oil Stadium · Indianapolis, IN |
| 11 | Sun Nov 17 | atJets | W28-27 | 5-6 | .455 | MetLife Stadium · East Rutherford, NJ |
| 12 | Sun Nov 24 | vsLions | L6-24 | 5-7 | .417 | Lucas Oil Stadium · Indianapolis, IN |
| 13 | Sun Dec 1 | atPatriots | W25-24 | 6-7 | .462 | Gillette Stadium · Foxborough, MA |
| --bye week-- |
| 15 | Sun Dec 15 | atBroncos | L13-31 | 6-8 | .429 | Empower Field at Mile High · Denver, CO |
| 16 | Sun Dec 22 | vsTitans | W38-30 | 7-8 | .467 | Lucas Oil Stadium · Indianapolis, IN |
| 17 | Sun Dec 29 | atGiants | L33-45 | 7-9 | .438 | MetLife Stadium · East Rutherford, NJ |
| 18 | Sun Jan 5 | vsJaguars | W26-23 (OT) | 8-9 | .471 | Lucas Oil Stadium · Indianapolis, IN |
