| PLAYER | G | ATT | YDS | AVG | LNG | TD | FUM | LST |
| James Cook III (BUF) | 15 | 287 | 1532 | 5.3 | 64 | 12 | 6 | 3 |
| Jonathan Taylor (IND) | 15 | 288 | 1489 | 5.2 | 83 | 17 | 1 | 1 |
| Derrick Henry (BAL) | 16 | 287 | 1469 | 5.1 | 59 | 16 | 4 | 3 |
| De'Von Achane (MIA) | 15 | 220 | 1267 | 5.8 | 59 | 8 | 1 | 0 |
| Bijan Robinson (ATL) | 15 | 250 | 1250 | 5.0 | 81 | 6 | 3 | 2 |
| Javonte Williams (DAL) | 16 | 252 | 1201 | 4.8 | 66 | 11 | 1 | 1 |
| Jahmyr Gibbs (DET) | 16 | 224 | 1143 | 5.1 | 78 | 13 | 2 | 1 |
| Kyren Williams (LAR) | 15 | 234 | 1100 | 4.7 | 34 | 10 | 2 | 2 |
| Saquon Barkley (PHI) | 15 | 261 | 1072 | 4.1 | 65 | 7 | 0 | 0 |
| Christian McCaffrey (SF) | 15 | 280 | 1039 | 3.7 | 24 | 9 | 1 | 0 |
| Rico Dowdle (CAR) | 15 | 217 | 1007 | 4.6 | 53 | 6 | 0 | 0 |
| Travis Etienne Jr. (JAX) | 15 | 229 | 999 | 4.4 | 71 | 7 | 0 | 0 |
| D'Andre Swift (CHI) | 14 | 204 | 993 | 4.9 | 25 | 7 | 2 | 2 |
| Breece Hall (NYJ) | 15 | 229 | 954 | 4.2 | 35 | 3 | 2 | 2 |
| Tony Pollard (TEN) | 15 | 210 | 949 | 4.5 | 65 | 5 | 3 | 2 |
| Josh Jacobs (GB) | 15 | 234 | 929 | 4.0 | 40 | 13 | 3 | 2 |
| Kenneth Walker III (SEA) | 15 | 190 | 879 | 4.6 | 55 | 5 | 0 | 0 |
| Chase Brown (CIN) | 15 | 197 | 846 | 4.3 | 37 | 4 | 1 | 0 |
| Jaylen Warren (PIT) | 14 | 185 | 828 | 4.5 | 45 | 6 | 0 | 0 |
| Ashton Jeanty (LV) | 15 | 224 | 828 | 3.7 | 64 | 5 | 1 | 1 |
| Quinshon Judkins (CLE) | 14 | 230 | 827 | 3.6 | 46 | 7 | 0 | 0 |
| TreVeyon Henderson (NE) | 15 | 148 | 776 | 5.2 | 69 | 7 | 1 | 1 |
| Jacory Croskey-Merritt (WSH) | 16 | 162 | 776 | 4.8 | 72 | 8 | 3 | 2 |
| J.K. Dobbins (DEN) | 10 | 153 | 772 | 5.0 | 41 | 4 | 0 | 0 |
| Kyle Monangai (CHI) | 15 | 155 | 731 | 4.7 | 39 | 5 | 0 | 0 |