Franchise 77 seasons 609–519–14 all-time 30 playoff trips 5 Super Bowls
2021 players
Passing
| Jimmy Garoppolo | 441 | 301 | 3,810 | 20 | 12 | 8.6 |
| Trey Lance | 71 | 41 | 603 | 5 | 2 | 8.5 |
| Deebo Samuel Sr. | 2 | 1 | 24 | 1 | 0 | 12.0 |
Rushing
| Elijah Mitchell | 207 | 963 | 5 | 4.7 |
| Deebo Samuel Sr. | 59 | 365 | 8 | 6.2 |
| Jeff Wilson | 79 | 294 | 2 | 3.7 |
| Trey Lance | 38 | 168 | 1 | 4.4 |
| Trey Sermon | 41 | 167 | 1 | 4.1 |
| JaMycal Hasty | 16 | 68 | 1 | 4.2 |
| Jimmy Garoppolo | 38 | 51 | 3 | 1.3 |
| Kyle Juszczyk | 8 | 22 | 1 | 2.8 |
| Raheem Mostert | 2 | 20 | 0 | 10.0 |
| George Kittle | 3 | 20 | 0 | 6.7 |
| Brandon Aiyuk | 5 | 17 | 0 | 3.4 |
| Jacques Patrick | 2 | 12 | 0 | 6.0 |
| Trenton Cannon | 3 | 4 | 0 | 1.3 |
Receiving
| Deebo Samuel Sr. | 121 | 77 | 1,405 | 6 | 11.6 |
| George Kittle | 94 | 71 | 910 | 6 | 9.7 |
| Brandon Aiyuk | 84 | 56 | 826 | 5 | 9.8 |
| Kyle Juszczyk | 38 | 30 | 296 | 1 | 7.8 |
| Jauan Jennings | 38 | 24 | 282 | 5 | 7.4 |
| Mohamed Sanu | 24 | 15 | 177 | 0 | 7.4 |
| JaMycal Hasty | 29 | 23 | 157 | 0 | 5.4 |
| Elijah Mitchell | 20 | 19 | 137 | 1 | 6.8 |
| Trent Sherfield | 20 | 9 | 87 | 1 | 4.4 |
| Charlie Woerner | 6 | 5 | 52 | 0 | 8.7 |
| Ross Dwelley | 5 | 4 | 51 | 1 | 10.2 |
| Jeff Wilson | 8 | 7 | 31 | 0 | 3.9 |
| Trey Sermon | 4 | 3 | 26 | 0 | 6.5 |