| PLAYER | G | ATT | YDS | AVG | LNG | TD | FUM | LST |
| James Cook III (BUF) | 17 | 309 | 1621 | 5.2 | 64 | 12 | 6 | 3 |
| Derrick Henry (BAL) | 17 | 307 | 1595 | 5.2 | 59 | 16 | 4 | 3 |
| Jonathan Taylor (IND) | 17 | 323 | 1585 | 4.9 | 83 | 18 | 1 | 1 |
| Bijan Robinson (ATL) | 17 | 287 | 1478 | 5.1 | 93 | 7 | 3 | 2 |
| De'Von Achane (MIA) | 16 | 238 | 1350 | 5.7 | 59 | 8 | 1 | 0 |
| Kyren Williams (LAR) | 17 | 259 | 1252 | 4.8 | 34 | 10 | 2 | 2 |
| Jahmyr Gibbs (DET) | 17 | 243 | 1223 | 5.0 | 78 | 13 | 2 | 1 |
| Christian McCaffrey (SF) | 17 | 311 | 1202 | 3.9 | 41 | 10 | 1 | 0 |
| Javonte Williams (DAL) | 16 | 252 | 1201 | 4.8 | 66 | 11 | 1 | 1 |
| Saquon Barkley (PHI) | 16 | 280 | 1140 | 4.1 | 65 | 7 | 0 | 0 |
| Travis Etienne Jr. (JAX) | 17 | 260 | 1107 | 4.3 | 71 | 7 | 0 | 0 |
| D'Andre Swift (CHI) | 16 | 223 | 1087 | 4.9 | 25 | 9 | 2 | 2 |
| Tony Pollard (TEN) | 17 | 242 | 1082 | 4.5 | 65 | 5 | 3 | 2 |
| Rico Dowdle (CAR) | 17 | 236 | 1076 | 4.6 | 53 | 6 | 1 | 1 |
| Breece Hall (NYJ) | 16 | 243 | 1065 | 4.4 | 59 | 4 | 2 | 2 |
| Kenneth Walker III (SEA) | 17 | 221 | 1027 | 4.6 | 55 | 5 | 0 | 0 |
| Chase Brown (CIN) | 17 | 232 | 1019 | 4.4 | 37 | 6 | 1 | 0 |
| Ashton Jeanty (LV) | 17 | 266 | 975 | 3.7 | 64 | 5 | 1 | 1 |
| Jaylen Warren (PIT) | 16 | 211 | 958 | 4.5 | 45 | 6 | 1 | 0 |
| Josh Jacobs (GB) | 15 | 234 | 929 | 4.0 | 40 | 13 | 3 | 2 |
| TreVeyon Henderson (NE) | 17 | 180 | 911 | 5.1 | 69 | 9 | 1 | 1 |
| Quinshon Judkins (CLE) | 14 | 230 | 827 | 3.6 | 46 | 7 | 0 | 0 |
| Jacory Croskey-Merritt (WSH) | 17 | 175 | 805 | 4.6 | 72 | 8 | 3 | 2 |
| Kyle Monangai (CHI) | 17 | 169 | 783 | 4.6 | 39 | 5 | 0 | 0 |
| J.K. Dobbins (DEN) | 10 | 153 | 772 | 5.0 | 41 | 4 | 0 | 0 |