| 1 | Sun Sep 7 | at Patriots | W20-13 | 1-0 | 1.000 | Gillette Stadium · Foxborough, MA |
| 2 | Mon Sep 15 | vsChargers | L9-20 | 1-1 | .500 | Allegiant Stadium · Las Vegas, NV |
| 3 | Sun Sep 21 | atCommanders | L24-41 | 1-2 | .333 | FedEx Field · North Englewood, MD |
| 4 | Sun Sep 28 | vsBears | L24-25 | 1-3 | .250 | Allegiant Stadium · Las Vegas, NV |
| 5 | Sun Oct 5 | atColts | L6-40 | 1-4 | .200 | Lucas Oil Stadium · Indianapolis, IN |
| 6 | Sun Oct 12 | vsTitans | W20-10 | 2-4 | .333 | Allegiant Stadium · Las Vegas, NV |
| 7 | Sun Oct 19 | atChiefs | L0-31 | 2-5 | .286 | Arrowhead Stadium · Kansas City, MO |
| --bye week-- |
| 9 | Sun Nov 2 | vsJaguars | L29-30 (OT) | 2-6 | .250 | Allegiant Stadium · Las Vegas, NV |
| 10 | Thu Nov 6 | atBroncos | L7-10 | 2-7 | .222 | Empower Field at Mile High · Denver, CO |
| 11 | Mon Nov 17 | vsCowboys | L16-33 | 2-8 | .200 | Allegiant Stadium · Las Vegas, NV |
| 12 | Sun Nov 23 | vsBrowns | L10-24 | 2-9 | .182 | Allegiant Stadium · Las Vegas, NV |
| 13 | Sun Nov 30 | atChargers | L14-31 | 2-10 | .167 | SoFi Stadium · Inglewood, CA |
| 14 | Sun Dec 7 | vsBroncos | L17-24 | 2-11 | .154 | Allegiant Stadium · Las Vegas, NV |
| 15 | Sun Dec 14 | atEagles | L0-31 | 2-12 | .143 | Lincoln Financial Field · Philadelphia, PA |
| 16 | Sun Dec 21 | atTexans | L21-23 | 2-13 | .133 | NRG Stadium · Houston, TX |
| 17 | Sun Dec 28 | vsGiants | L10-34 | 2-14 | .125 | Allegiant Stadium · Las Vegas, NV |
| 18 | Sun Jan 4 | vsChiefs | W14-12 | 3-14 | .176 | Allegiant Stadium · Las Vegas, NV |
