| # | Player | Team | G | ATT | YDS ▾ | Y/C | TD | FUM | EPA |
|---|---|---|---|---|---|---|---|---|---|
| 1 | James Cook | BUF | 17 | 309 | 1621 | 5.2 | 12 | 6 | 5.6 |
| 2 | Derrick Henry | BAL | 17 | 307 | 1595 | 5.2 | 16 | 4 | 9.2 |
| 3 | Jonathan Taylor | IND | 17 | 323 | 1585 | 4.9 | 18 | 1 | 18.8 |
| 4 | Bijan Robinson | ATL | 17 | 287 | 1478 | 5.1 | 7 | 3 | -12.3 |
| 5 | De'Von Achane | MIA | 16 | 238 | 1350 | 5.7 | 8 | 1 | 14.0 |
| 6 | Kyren Williams | LA | 17 | 259 | 1252 | 4.8 | 10 | 2 | 4.9 |
| 7 | Jahmyr Gibbs | DET | 17 | 243 | 1223 | 5.0 | 13 | 2 | -2.7 |
| 8 | Christian McCaffrey | SF | 17 | 311 | 1202 | 3.9 | 10 | 1 | -21.1 |
| 9 | Javonte Williams | DAL | 16 | 252 | 1201 | 4.8 | 11 | 1 | 12.2 |
| 10 | Saquon Barkley | PHI | 16 | 280 | 1140 | 4.1 | 7 | 0 | -24.1 |
| 11 | Travis Etienne | JAX | 17 | 260 | 1107 | 4.3 | 7 | 0 | -19.0 |
| 12 | D'Andre Swift | CHI | 16 | 223 | 1087 | 4.9 | 9 | 2 | 15.4 |
| 13 | Tony Pollard | TEN | 17 | 242 | 1082 | 4.5 | 5 | 3 | -21.7 |
| 14 | Rico Dowdle | CAR | 17 | 236 | 1076 | 4.6 | 6 | 1 | -2.3 |
| 15 | Breece Hall | NYJ | 16 | 243 | 1065 | 4.4 | 4 | 2 | -22.3 |
| 16 | Kenneth Walker III | SEA | 17 | 221 | 1027 | 4.6 | 5 | 0 | -14.3 |
| 17 | Chase Brown | CIN | 17 | 232 | 1019 | 4.4 | 6 | 1 | -4.2 |
| 18 | Ashton Jeanty | LV | 17 | 266 | 975 | 3.7 | 5 | 1 | -65.2 |
| 19 | Jaylen Warren | PIT | 16 | 211 | 958 | 4.5 | 6 | 1 | -0.5 |
| 20 | Josh Jacobs | GB | 15 | 234 | 929 | 4.0 | 13 | 3 | -14.8 |
| 21 | TreVeyon Henderson | NE | 17 | 180 | 911 | 5.1 | 9 | 1 | 8.4 |
| 22 | Quinshon Judkins | CLE | 14 | 230 | 827 | 3.6 | 7 | 0 | -25.1 |
| 23 | Jacory Croskey-Merritt | WAS | 17 | 175 | 805 | 4.6 | 8 | 3 | -6.5 |
| 24 | Kyle Monangai | CHI | 17 | 169 | 783 | 4.6 | 5 | 0 | 3.7 |
| 25 | J.K. Dobbins | DEN | 10 | 153 | 772 | 5.0 | 4 | 0 | 4.2 |
| 26 | Jordan Mason | MIN | 16 | 159 | 758 | 4.8 | 6 | 2 | -5.8 |
| 27 | Blake Corum | LA | 17 | 145 | 746 | 5.1 | 6 | 0 | 15.9 |
| 28 | Tyrone Tracy Jr. | NYG | 15 | 176 | 740 | 4.2 | 2 | 0 | -9.8 |
| 29 | Zach Charbonnet | SEA | 16 | 184 | 730 | 4.0 | 12 | 0 | -1.2 |
| 30 | David Montgomery | DET | 17 | 158 | 716 | 4.5 | 8 | 2 | -0.6 |
| 31 | Woody Marks | HOU | 16 | 196 | 703 | 3.6 | 2 | 1 | -29.2 |
| 32 | Kimani Vidal | LAC | 13 | 155 | 643 | 4.1 | 3 | 1 | -14.1 |
| 33 | Kareem Hunt | KC | 17 | 163 | 611 | 3.7 | 8 | 2 | 9.7 |
| 34 | Rhamondre Stevenson | NE | 14 | 130 | 603 | 4.6 | 7 | 2 | -18.3 |
| 35 | Bucky Irving | TB | 10 | 173 | 588 | 3.4 | 1 | 1 | -35.6 |
| 36 | Josh Allen | BUF | 16 | 112 | 579 | 5.2 | 14 | 6 | 38.8 |
| 37 | Rachaad White | TB | 17 | 132 | 572 | 4.3 | 4 | 0 | 10.4 |
| 38 | Aaron Jones | MIN | 12 | 132 | 548 | 4.2 | 2 | 0 | -2.4 |
| 39 | Omarion Hampton | LAC | 9 | 124 | 545 | 4.4 | 4 | 0 | -0.8 |
| 40 | RJ Harvey | DEN | 17 | 146 | 540 | 3.7 | 7 | 1 | -22.9 |
| 41 | Kenny Gainwell | PIT | 17 | 114 | 537 | 4.7 | 5 | 1 | -0.7 |
| 42 | Tyler Allgeier | ATL | 17 | 143 | 514 | 3.6 | 8 | 0 | -11.6 |
| 43 | Chuba Hubbard | CAR | 15 | 134 | 511 | 3.8 | 1 | 1 | -15.7 |
| 44 | Nick Chubb | HOU | 15 | 122 | 506 | 4.1 | 3 | 0 | -13.6 |
| 45 | Chris Rodriguez Jr. | WAS | 12 | 112 | 500 | 4.5 | 6 | 0 | 6.2 |
| 46 | Justin Herbert | LAC | 16 | 83 | 498 | 6.0 | 2 | 4 | 15.9 |
| 47 | Emanuel Wilson | GB | 17 | 125 | 496 | 4.0 | 3 | 0 | -7.7 |
| 48 | Jaxson Dart | NYG | 14 | 86 | 487 | 5.7 | 9 | 3 | 38.1 |
| 49 | Alvin Kamara | NO | 11 | 131 | 471 | 3.6 | 1 | 1 | -28.8 |
| 50 | Isiah Pacheco | KC | 13 | 118 | 462 | 3.9 | 1 | 0 | -13.6 |
335 players