The San Francisco 49ers have a 6-8 record in the regular-season and playoffs versus the Bills all-time.
| TEAM | DATE | REC | TM | OPP | RESULT | W% | TD | 1DWN | OFF | OPP OFF | 3DWN% | 4DWN% | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 |  | 49ers | 9/24/1972 | 0-1 | @ | L 20-27 | .000 | 2 | 10 | 202 | 233 | ||||
| 2 | | 49ers | 12/21/1980 | 0-1 | vs | L 13-18 | .000 | 2 | 19 | 298 | 267 | ||||
| 3 | | 49ers | 12/11/1983 | 1-0 | @ | W 23-10 | 1.000 | 2 | 19 | 310 | 303 | ||||
| 4 | | 49ers | 12/17/1989 | 1-0 | vs | W 21-10 | 1.000 | 3 | 18 | 283 | 301 | ||||
| 5 | | 49ers | 9/13/1992 | 0-1 | vs | L 31-34 | .000 | 4 | 26 | 598 | 488 | 61.5 | 100.0 | ||
| 6 | | 49ers | 12/3/1995 | 1-0 | vs | W 27-17 | 1.000 | 3 | 18 | 323 | 275 | 31.3 | 50.0 | ||
| 7 | | 49ers | 10/4/1998 | 0-1 | @ | L 21-26 | .000 | 3 | 23 | 377 | 352 | 46.2 | |||
| 8 | | 49ers | 12/2/2001 | 1-0 | vs | W 35-0 | 1.000 | 5 | 26 | 409 | 191 | 66.7 | 0.0 | ||
| 9 | | 49ers | 12/26/2004 | 0-1 | vs | L 7-41 | .000 | 1 | 12 | 189 | 441 | 30.0 | 100.0 | ||
| 10 | | 49ers | 11/30/2008 | 1-0 | @ | W 10-3 | 1.000 | 1 | 12 | 195 | 350 | 46.7 | |||
| 11 | | 49ers | 10/7/2012 | 1-0 | vs | W 45-3 | 1.000 | 6 | 29 | 621 | 204 | 63.6 | 100.0 | ||
| 12 | | 49ers | 10/16/2016 | 0-1 | @ | L 16-45 | .000 | 1 | 16 | 300 | 492 | 23.1 | 0.0 | ||
| 13 | | 49ers | 12/7/2020 | 0-1 | vs | L 24-34 | .000 | 3 | 24 | 402 | 449 | 54.5 | 0.0 | ||
| 14 | | 49ers | 12/1/2024 | 0-1 | @ | L 10-35 | .000 | 1 | 15 | 239 | 372 | 30.0 | 100.0 | ||
| Average | .429 | 2.6 | 19.1 | 339.0 | 337.0 | ||||||||||
| Total | 6-8 | .429 | 37 | 267 | 4,746 | 4,718 |
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Team Leaders 
PASS
2,151
Jones
RUSH
922
McCaffrey
REC
820
McCaffrey
Team Rankings
PPG
24.6
11th
OPP PPG
20.9
11th
RUSH YDS/G
101.4
25th
PASS YDS/G
256.6
6th
Seahawks
IND
CHI
NFL 2025 Leaders
NFL 2025 Rankings
NFL Fantasy 2025
NFL 2025 Betting
NFL 2025 Standings
| AFC East | W | L | T | PCT |
|---|---|---|---|---|
11 | 3 | 0 | .786 | |
10 | 4 | 0 | .714 | |
 Dolphins - e | 6 | 8 | 0 | .429 |
 Jets - e | 3 | 11 | 0 | .214 |
| AFC North | W | L | T | PCT |
8 | 6 | 0 | .571 | |
7 | 7 | 0 | .500 | |
 Bengals - e | 4 | 10 | 0 | .286 |
 Browns - e | 3 | 11 | 0 | .214 |
| AFC South | W | L | T | PCT |
10 | 4 | 0 | .714 | |
9 | 5 | 0 | .643 | |
8 | 6 | 0 | .571 | |
 Titans - e | 2 | 12 | 0 | .143 |
| AFC West | W | L | T | PCT |
 Broncos - x | 12 | 2 | 0 | .857 |
10 | 4 | 0 | .714 | |
 Chiefs - e | 6 | 8 | 0 | .429 |
 Raiders - e | 2 | 12 | 0 | .143 |
Patriots
Steelers
Ravens
Jaguars
Texans
Chargers| NFC East | W | L | T | PCT |
|---|---|---|---|---|
9 | 5 | 0 | .643 | |
6 | 7 | 1 | .464 | |
 Commanders - e | 4 | 10 | 0 | .286 |
 Giants - e | 2 | 12 | 0 | .143 |
| NFC North | W | L | T | PCT |
10 | 4 | 0 | .714 | |
9 | 4 | 1 | .679 | |
8 | 6 | 0 | .571 | |
 Vikings - e | 6 | 8 | 0 | .429 |
| NFC South | W | L | T | PCT |
7 | 7 | 0 | .500 | |
7 | 7 | 0 | .500 | |
 Falcons - e | 5 | 9 | 0 | .357 |
 Saints - e | 4 | 10 | 0 | .286 |
| NFC West | W | L | T | PCT |
12 | 3 | 0 | .800 | |
 Rams - x | 11 | 4 | 0 | .733 |
10 | 4 | 0 | .714 | |
 Cardinals - e | 3 | 11 | 0 | .214 |
Eagles
Cowboys
Packers
Lions
Buccaneers
Panthers
