| 1 | Sun Sep 13 | at Panthers | W34-30 | 1-0 | 1.000 | Bank of America Stadium · Charlotte, NC |
| 2 | Mon Sep 21 | vsSaints | W34-24 | 2-0 | 1.000 | Allegiant Stadium · Las Vegas, NV |
| 3 | Sun Sep 27 | atPatriots | L20-36 | 2-1 | .667 | Gillette Stadium · Foxborough, MA |
| 4 | Sun Oct 4 | vsBills | L23-30 | 2-2 | .500 | Allegiant Stadium · Las Vegas, NV |
| 5 | Sun Oct 11 | atChiefs | W40-32 | 3-2 | .600 | Arrowhead Stadium · Kansas City, MO |
| --bye week-- |
| 7 | Sun Oct 25 | vsBuccaneers | L20-45 | 3-3 | .500 | Allegiant Stadium · Las Vegas, NV |
| 8 | Sun Nov 1 | atBrowns | W16-6 | 4-3 | .571 | FirstEnergy Stadium · Cleveland, OH |
| 9 | Sun Nov 8 | atChargers | W31-26 | 5-3 | .625 | SoFi Stadium · Inglewood, CA |
| 10 | Sun Nov 15 | vsBroncos | W37-12 | 6-3 | .667 | Allegiant Stadium · Las Vegas, NV |
| 11 | Sun Nov 22 | vsChiefs | L31-35 | 6-4 | .600 | Allegiant Stadium · Las Vegas, NV |
| 12 | Sun Nov 29 | atFalcons | L6-43 | 6-5 | .545 | Mercedes-Benz Stadium · Atlanta, GA |
| 13 | Sun Dec 6 | atJets | W31-28 | 7-5 | .583 | MetLife Stadium · East Rutherford, NJ |
| 14 | Sun Dec 13 | vsColts | L27-44 | 7-6 | .538 | Allegiant Stadium · Las Vegas, NV |
| 15 | Thu Dec 17 | vsChargers | L27-30 (OT) | 7-7 | .500 | Allegiant Stadium · Las Vegas, NV |
| 16 | Sat Dec 26 | vsDolphins | L25-26 | 7-8 | .467 | Allegiant Stadium · Las Vegas, NV |
| 17 | Sun Jan 3 | atBroncos | W32-31 | 8-8 | .500 | Empower Field at Mile High · Denver, CO |
