| Name | Team | Comp | Att | Pct | Yds | Y/G | Y/A | TD | Int | Sacks | YdsL |
| Drew Brees | NOR | 413 | 635 | 65 | 5069 | 316.8 | 8 | 34 | 17 | 13 | 92 |
| Kurt Warner | ARI | 401 | 598 | 67.1 | 4583 | 286.4 | 7.7 | 30 | 14 | 26 | 182 |
| Jay Cutler | DEN | 384 | 616 | 62.3 | 4526 | 282.9 | 7.3 | 25 | 18 | 11 | 69 |
| Matt Schaub | HOU | 251 | 380 | 66.1 | 3043 | 276.6 | 8 | 15 | 10 | 23 | 149 |
| Tony Romo | DAL | 276 | 450 | 61.3 | 3448 | 265.2 | 7.7 | 26 | 14 | 20 | 123 |
| Aaron Rodgers | GNB | 341 | 536 | 63.6 | 4038 | 252.4 | 7.5 | 28 | 13 | 34 | 231 |
| Philip Rivers | SDG | 312 | 478 | 65.3 | 4009 | 250.6 | 8.4 | 34 | 11 | 25 | 151 |
| Peyton Manning | IND | 371 | 555 | 66.8 | 4002 | 250.1 | 7.2 | 27 | 12 | 14 | 86 |
| Donovan McNabb | PHI | 345 | 571 | 60.4 | 3916 | 244.8 | 6.9 | 23 | 11 | 23 | 149 |
| Sage Rosenfels | HOU | 116 | 174 | 66.7 | 1431 | 238.5 | 8.2 | 6 | 10 | 9 | 58 |
| Matt Cassel | NWE | 327 | 516 | 63.4 | 3693 | 230.8 | 7.2 | 21 | 11 | 47 | 219 |
| Chad Pennington | MIA | 321 | 476 | 67.4 | 3653 | 228.3 | 7.7 | 19 | 7 | 24 | 121 |
| Shaun Hill | SFO | 181 | 288 | 62.8 | 2046 | 227.3 | 7.1 | 13 | 8 | 23 | 148 |
| David Garrard | JAC | 335 | 535 | 62.6 | 3620 | 226.3 | 6.8 | 15 | 13 | 42 | 288 |
| Jeff Garcia | TAM | 244 | 376 | 64.9 | 2712 | 226 | 7.2 | 12 | 6 | 23 | 100 |
| Brett Favre | NYJ | 343 | 522 | 65.7 | 3472 | 217 | 6.7 | 22 | 22 | 30 | 213 |
| Matt Ryan | ATL | 265 | 434 | 61.1 | 3440 | 215 | 7.9 | 16 | 11 | 17 | 104 |
| Brian Griese | TAM | 110 | 184 | 59.8 | 1073 | 214.6 | 5.8 | 5 | 7 | 9 | 69 |
| Ben Roethlisberger | PIT | 281 | 469 | 59.9 | 3301 | 206.3 | 7 | 17 | 15 | 46 | 284 |
| Jake Delhomme | CAR | 246 | 414 | 59.4 | 3288 | 205.5 | 7.9 | 15 | 12 | 20 | 130 |
| Jason Campbell | WAS | 315 | 506 | 62.3 | 3245 | 202.8 | 6.4 | 13 | 6 | 38 | 266 |
| Eli Manning | NYG | 289 | 479 | 60.3 | 3238 | 202.4 | 6.8 | 21 | 10 | 27 | 174 |
| Kyle Orton | CHI | 272 | 465 | 58.5 | 2972 | 198.1 | 6.4 | 18 | 12 | 27 | 160 |
| Gus Frerotte | MIN | 178 | 301 | 59.1 | 2157 | 196.1 | 7.2 | 12 | 15 | 29 | 164 |
| Trent Edwards | BUF | 245 | 374 | 65.5 | 2699 | 192.8 | 7.2 | 11 | 10 | 23 | 143 |
| Jon Kitna | DET | 68 | 120 | 56.7 | 758 | 189.5 | 6.3 | 5 | 5 | 15 | 89 |
| J.T. O'Sullivan | SFO | 128 | 220 | 58.2 | 1678 | 186.4 | 7.6 | 8 | 11 | 32 | 197 |
| Tyler Thigpen | KAN | 230 | 420 | 54.8 | 2608 | 186.3 | 6.2 | 18 | 12 | 26 | 162 |
| Joe Flacco | BAL | 257 | 428 | 60 | 2971 | 185.7 | 6.9 | 14 | 12 | 32 | 276 |
| Carson Palmer | CIN | 75 | 129 | 58.1 | 731 | 182.8 | 5.7 | 3 | 4 | 11 | 67 |
| Marc Bulger | STL | 251 | 440 | 57 | 2720 | 181.3 | 6.2 | 11 | 13 | 38 | 263 |
