| Regular Season: Week 1 |
 Steelers |
at |
 Bills |
Sunday, September 12, 2021 |
1:00PM |
PIT 23, BUF 16 |
| Regular Season: Week 2 |
Bills |
at |
 Dolphins |
Sunday, September 19, 2021 |
1:00PM |
BUF 35, MIA 0 |
| Regular Season: Week 3 |
 Washington |
at |
Bills |
Sunday, September 26, 2021 |
1:00PM |
WSH 21, BUF 43 |
| Regular Season: Week 4 |
 Texans |
at |
Bills |
Sunday, October 3, 2021 |
1:00PM |
HOU 0, BUF 40 |
| Regular Season: Week 5 |
Bills |
at |
 Chiefs |
Sunday, October 10, 2021 |
8:20PM |
BUF 38, KC 20 |
| Regular Season: Week 6 |
Bills |
at |
 Titans |
Monday, October 18, 2021 |
8:15PM |
BUF 31, TEN 34 |
| Regular Season: Week 8 |
Dolphins |
at |
Bills |
Sunday, October 31, 2021 |
1:00PM |
MIA 11, BUF 26 |
| Regular Season: Week 9 |
Bills |
at |
 Jaguars |
Sunday, November 7, 2021 |
1:00PM |
BUF 6, JAX 9 |
| Regular Season: Week 10 |
Bills |
at |
 Jets |
Sunday, November 14, 2021 |
1:00PM |
BUF 45, NYJ 17 |
| Regular Season: Week 11 |
 Colts |
at |
Bills |
Sunday, November 21, 2021 |
1:00PM |
IND 41, BUF 15 |
| Regular Season: Week 12 |
Bills |
at |
 Saints |
Thursday, November 25, 2021 |
8:20PM |
BUF 31, NO 6 |
| Regular Season: Week 13 |
 Patriots |
at |
Bills |
Monday, December 6, 2021 |
8:15PM |
NE 14, BUF 10 |
| Regular Season: Week 14 |
Bills |
at |
 Buccaneers |
Sunday, December 12, 2021 |
4:25PM |
BUF 27, TB 33 |
| Regular Season: Week 15 |
 Panthers |
at |
Bills |
Sunday, December 19, 2021 |
TBD |
CAR 14, BUF 31 |
| Regular Season: Week 16 |
Bills |
at |
Patriots |
Sunday, December 26, 2021 |
1:00PM |
BUF 33, NE 21 |
| Regular Season: Week 17 |
 Falcons |
at |
Bills |
Sunday, January 2, 2022 |
1:00PM |
ATL 15, BUF 29 |
| Regular Season: Week 18 |
Jets |
at |
Bills |
Sunday, January 9, 2022 |
1:00PM |
NYJ 10, BUF 27 |