Schedule
| Week | Date | Kickoff (ET) | TV | Opponent | Result | Record | Game Site | NFL.com Recap |
|---|---|---|---|---|---|---|---|---|
| 1 | Sunday September 7 | 1:00 PM | Fox | Seattle Seahawks | W 34–10 | 1–0 | Ralph Wilson Stadium | Recap |
| 2 | Sunday September 14 | 1:00 PM | CBS | at Jacksonville Jaguars | W 20–16 | 2–0 | Jacksonville Municipal Stadium | Recap |
| 3 | Sunday September 21 | 1:00 PM | CBS | Oakland Raiders | W 24–23 | 3–0 | Ralph Wilson Stadium | Recap |
| 4 | Sunday September 28 | 4:05 PM | CBS | at St. Louis Rams | W 31–14 | 4–0 | Edward Jones Dome | Recap |
| 5 | Sunday October 5 | 4:15 PM | CBS | at Arizona Cardinals | L 41–17 | 4–1 | University of Phoenix Stadium | Recap |
| 6 | Bye Week | |||||||
| 7 | Sunday October 19 | 1:00 PM | CBS | San Diego Chargers | W 23–14 | 5–1 | Ralph Wilson Stadium | Recap |
| 8 | Sunday October 26 | 1:00 PM | CBS | at Miami Dolphins | L 25–16 | 5–2 | Dolphin Stadium | Recap |
| 9 | Sunday November 2 | 1:00 PM | CBS | New York Jets | L 26–17 | 5–3 | Ralph Wilson Stadium | Recap |
| 10 | Sunday November 9 | 1:00 PM | CBS | at New England Patriots | L 20–10 | 5–4 | Gillette Stadium | Recap |
| 11 | Monday November 17 | 8:30 PM | ESPN | Cleveland Browns | L 29–27 | 5–5 | Ralph Wilson Stadium | Recap |
| 12 | Sunday November 23 | 1:00 PM | CBS | at Kansas City Chiefs | W 54–31 | 6–5 | Arrowhead Stadium | Recap |
| 13 | Sunday November 30 | 1:00 PM | Fox | San Francisco 49ers | L 10–3 | 6–6 | Ralph Wilson Stadium | Recap |
| 14 | Sunday December 7 | 4:05 PM | CBS | Miami Dolphins | L 16–3 | 6–7 | Rogers Centre (Toronto) | Recap |
| 15 | Sunday December 14 | 1:00 PM* | CBS | at New York Jets | L 31–27 | 6–8 | Giants Stadium | Recap |
| 16 | Sunday December 21 | 4:05 PM* | CBS | at Denver Broncos | W 30–23 | 7–8 | Invesco Field at Mile High | Recap |
| 17 | Sunday December 28 | 1:00 PM* | CBS | New England Patriots | L 13–0 | 7–9 | Ralph Wilson Stadium | Recap |
- Green background indicates win.
- Red background indicates loss.
- An asterisk (*) indicates games potentially moved to Sunday Night Football due to flex scheduling.
One regular season home game per year will be played at the Rogers Centre in Toronto, Ontario as part of a five-year deal. For 2008, December 7's matchup with the Miami Dolphins was staged in Toronto.
Read more about this topic: 2008 Buffalo Bills Season