Russell Wilson has a passer rating of 98.9 with 4,353 yards, 36 touchdowns and 10 interceptions in 21 games against the 49ers in his career.
| NAME | DATE | TM | OPP | CMP | ATT | PCT | YDS | AVG | TD | TD% | INT | INT% | SCK | SCKY | RATE | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
 | Russell Wilson | 10/18/2012 |  SEA | @ |  SF | 9 | 23 | 39.1 | 122 | 5.3 | 0 | 0.0 | 1 | 4.3 | 2 | 7 | 38.7 |
| | Russell Wilson | 12/23/2012 | SEA | vs | SF | 15 | 21 | 71.4 | 171 | 8.1 | 4 | 19.0 | 1 | 4.8 | 1 | 1 | 115.3 |
| | Russell Wilson | 9/15/2013 | SEA | vs | SF | 8 | 19 | 42.1 | 142 | 7.5 | 1 | 5.3 | 1 | 5.3 | 4 | 24 | 63.9 |
| | Russell Wilson | 12/8/2013 | SEA | @ | SF | 15 | 25 | 60.0 | 199 | 8.0 | 1 | 4.0 | 1 | 4.0 | 2 | 21 | 81.9 |
| | Russell Wilson | 11/27/2014 | SEA | @ | SF | 15 | 22 | 68.2 | 236 | 10.7 | 1 | 4.5 | 0 | 0.0 | 4 | 14 | 118.8 |
| | Russell Wilson | 12/14/2014 | SEA | vs | SF | 12 | 24 | 50.0 | 168 | 7.0 | 1 | 4.2 | 1 | 4.2 | 5 | 30 | 69.4 |
| | Russell Wilson | 10/22/2015 | SEA | @ | SF | 18 | 24 | 75.0 | 235 | 9.8 | 1 | 4.2 | 2 | 8.3 | 5 | 23 | 84.5 |
| | Russell Wilson | 11/22/2015 | SEA | vs | SF | 24 | 29 | 82.8 | 260 | 9.0 | 3 | 10.3 | 0 | 0.0 | 2 | 7 | 138.5 |
| | Russell Wilson | 9/25/2016 | SEA | vs | SF | 15 | 23 | 65.2 | 243 | 10.6 | 1 | 4.3 | 0 | 0.0 | 2 | 17 | 114.9 |
| | Russell Wilson | 1/1/2017 | SEA | @ | SF | 19 | 32 | 59.4 | 258 | 8.1 | 1 | 3.1 | 0 | 0.0 | 1 | 6 | 95.6 |
| | Russell Wilson | 9/17/2017 | SEA | vs | SF | 23 | 39 | 59.0 | 198 | 5.1 | 1 | 2.6 | 0 | 0.0 | 3 | 17 | 80.9 |
| | Russell Wilson | 11/26/2017 | SEA | @ | SF | 20 | 34 | 58.8 | 228 | 6.7 | 2 | 5.9 | 1 | 2.9 | 0 | 0 | 86.4 |
| | Russell Wilson | 12/2/2018 | SEA | vs | SF | 11 | 17 | 64.7 | 185 | 10.9 | 4 | 23.5 | 0 | 0.0 | 3 | 22 | 140.9 |
| | Russell Wilson | 12/16/2018 | SEA | @ | SF | 23 | 31 | 74.2 | 237 | 7.6 | 2 | 6.5 | 0 | 0.0 | 3 | 20 | 117.3 |
| | Russell Wilson | 11/11/2019 | SEA | @ | SF | 24 | 34 | 70.6 | 232 | 6.8 | 1 | 2.9 | 1 | 2.9 | 5 | 43 | 86.9 |
| | Russell Wilson | 12/29/2019 | SEA | vs | SF | 25 | 40 | 62.5 | 233 | 5.8 | 2 | 5.0 | 0 | 0.0 | 1 | 10 | 95.1 |
| | Russell Wilson | 11/1/2020 | SEA | vs | SF | 27 | 37 | 73.0 | 261 | 7.1 | 4 | 10.8 | 0 | 0.0 | 2 | 12 | 128.3 |
| | Russell Wilson | 1/3/2021 | SEA | @ | SF | 20 | 36 | 55.6 | 181 | 5.0 | 2 | 5.6 | 0 | 0.0 | 2 | 22 | 87.8 |
| | Russell Wilson | 10/3/2021 | SEA | @ | SF | 16 | 23 | 69.6 | 149 | 6.5 | 2 | 8.7 | 0 | 0.0 | 3 | 20 | 116.0 |
| | Russell Wilson | 12/5/2021 | SEA | vs | SF | 30 | 37 | 81.1 | 231 | 6.2 | 2 | 5.4 | 1 | 2.7 | 4 | 50 | 99.4 |
 | Russell Wilson | 9/25/2022 |  DEN | vs | SF | 20 | 33 | 60.6 | 184 | 5.6 | 0 | 0.0 | 0 | 0.0 | 4 | 24 | 75.8 |
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