| Week | Date | Away | Home | Time (ET) |
| 1 | Thu, Sept. 8 | Bills | Rams | 8:20 p.m. |
| 2 | Mon, Sept. 19 | Titans | Bills | 7:15 p.m. |
| 3 | Sun, Sept. 25 | Bills | Dolphins | 1 p.m. |
| 4 | Sun, Oct. 2 | Bills | Ravens | 1 p.m. |
| 5 | Sun, Oct. 9 | Steelers | Bills | 1 p.m. |
| 6 | Sun, Oct. 16 | Bills | Chiefs | 4:25 p.m. |
| 7 | Sun, Oct. 23 | Bye | Bye | Bye |
| 8 | Sun, Oct. 30 | Packers | Bills | 8:20 p.m. |
| 9 | Sun, Nov. 6 | Bills | Jets | 1 p.m. |
| 10 | Sun, Nov. 13 | Vikings | Bills | 1 p.m. |
| 11 | Sun, Nov. 20 | Browns | Bills | 1 p.m. |
| 12 | Thu, Nov. 24 | Bills | Lions | 12:30 p.m. |
| 13 | Thu, Dec. 1 | Bills | Patriots | 8:15 p.m. |
| 14 | Sun, Dec. 11 | Jets | Bills | 1 p.m. |
| 15 | TBD | Dolphins | Bills | TBD |
| 16 | Sat, Dec. 24 | Bills | Bears | 1 p.m. |
| 17 | Mon, Jan. 2 | Bills | Bengals | 8:30 p.m. |
| 18 | TBD | Patriots | Bills | TBD |
