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| Single-Season ERA Leaderboard | |
| * - Indicates Hall of Fame |
| Rank | Player | ERA | IP | Year | |
| 1. | Michael Nock | 2.223 | 194.3 | 2006 | |
| 2. | Samuel Scull | 2.630 | 232.7 | 2005 | |
| 3. | Lawrence Rosol | 2.696 | 227.0 | 2006 | |
| 4. | Freddy Berenguer | 2.930 | 199.7 | 2005 | |
| 5. | Stanford Hinton | 2.946 | 223.0 | 2005 | |
| 6. | Richard Coburn | 2.970 | 236.3 | 2006 | |
| 7. | Estanis Delmonte | 3.058 | 223.7 | 2005 | |
| 8. | Stanford Hinton | 3.059 | 238.3 | 2006 | |
| 9. | Michael Nock | 3.059 | 203.0 | 2005 | |
| 10. | Samuel Grullon | 3.090 | 256.3 | 2005 | |
| 11. | Samuel Scull | 3.130 | 230.0 | 2006 | |
| 12. | Mario Benero | 3.145 | 200.3 | 2005 | |
| 13. | Robert Unrein | 3.190 | 237.0 | 2006 | |
| 14. | Richard Fumihiro | 3.258 | 240.3 | 2005 | |
| 15. | Ken Newman | 3.268 | 168.0 | 2006 | |
| 16. | Numbers Hight | 3.269 | 201.0 | 2005 | |
| 17. | Robert Haire | 3.301 | 242.7 | 2005 | |
| 18. | Robert Haire | 3.314 | 239.0 | 2006 | |
| 19. | Leon Santana | 3.317 | 211.7 | 2005 | |
| 20. | Freddy Berenguer | 3.326 | 230.0 | 2006 | |
| Donald Denney | 3.326 | 184.0 | 2005 | ||
| 22. | Joseph Seldon | 3.334 | 164.7 | 2005 | |
| 23. | Robert Danielson | 3.338 | 210.3 | 2005 | |
| 24. | Jose Davalos | 3.364 | 214.0 | 2006 | |
| 25. | Tenchi Takamori | 3.375 | 176.0 | 2006 | |
| 26. | Kenneth Vanburen | 3.375 | 202.7 | 2005 | |
| 27. | Alexander Godinez | 3.426 | 220.7 | 2006 | |
| 28. | Clair Johnson | 3.430 | 246.7 | 2005 | |
| 29. | Lawrence Rosol | 3.440 | 225.0 | 2005 | |
| 30. | Alberto Castillo | 3.447 | 203.7 | 2006 | |
| 31. | Richard Coburn | 3.497 | 231.7 | 2005 | |
| 32. | Bernardo Reynoso | 3.501 | 241.7 | 2006 | |
| 33. | David Zeman | 3.506 | 197.7 | 2005 | |
| 34. | Chris West | 3.522 | 191.7 | 2006 | |
| 35. | Samuel Grullon | 3.525 | 217.0 | 2006 | |
| 36. | Donald Denney | 3.526 | 201.7 | 2006 | |
| 37. | Robert Unrein | 3.535 | 239.3 | 2005 | |
| 38. | Alexander Godinez | 3.552 | 223.0 | 2005 | |
| 39. | Jared Motoichi | 3.569 | 232.0 | 2005 | |
| 40. | Anthony Calderon | 3.572 | 234.3 | 2006 | |
| 41. | Bernardo Reynoso | 3.586 | 256.0 | 2005 | |
| 42. | Ernest Bohanon | 3.597 | 187.7 | 2006 | |
| 43. | Amadeo Martinez | 3.597 | 207.7 | 2005 | |
| 44. | Takitarou Bunrakuken | 3.616 | 219.0 | 2006 | |
| 45. | Thomas Borton | 3.628 | 235.7 | 2005 | |
| 46. | Gilbert Dillon | 3.641 | 207.7 | 2006 | |
| 47. | Jose Davalos | 3.654 | 221.7 | 2005 | |
| 48. | Camilo Briceno | 3.658 | 206.7 | 2006 | |
| 49. | Bricio Guarino | 3.668 | 211.0 | 2005 | |
| 50. | Alexander Deen | 3.680 | 217.7 | 2006 | |
| 51. | Anthony Chou | 3.688 | 212.3 | 2005 | |
| 52. | Troy Lindell | 3.688 | 190.3 | 2006 | |
| 53. | Charles Hitch | 3.708 | 206.3 | 2006 | |
| 54. | Juan Eames | 3.764 | 208.0 | 2005 | |
| 55. | Estanis Delmonte | 3.765 | 196.0 | 2006 | |
| 56. | Jeffery Paton | 3.794 | 204.0 | 2005 | |
| 57. | Thomas Borton | 3.809 | 186.7 | 2006 | |
| 58. | Kevin Grant | 3.811 | 196.0 | 2006 | |
| 59. | Archie Aubry | 3.829 | 228.0 | 2006 | |
| 60. | Julio Lozoya | 3.830 | 239.7 | 2005 | |
| 61. | Pablo Bustos | 3.839 | 211.0 | 2006 | |
| 62. | Daren Crook | 3.851 | 212.7 | 2005 | |
| 63. | Tokuichirou Kenzo | 3.864 | 202.7 | 2006 | |
| 64. | Steven Bristol | 3.876 | 204.3 | 2005 | |
| 65. | Numbers Hight | 3.877 | 190.3 | 2006 | |
| 66. | Victor Proctor | 3.895 | 205.7 | 2005 | |
| 67. | Julian Pereira | 3.941 | 246.7 | 2005 | |
| 68. | Joseph Seldon | 3.943 | 180.3 | 2006 | |
| 69. | Leon Santana | 3.945 | 175.7 | 2006 | |
| 70. | Alvaro Santana | 3.950 | 193.7 | 2006 | |
| 71. | Juan Eames | 3.953 | 214.0 | 2006 | |
| 72. | Clair Johnson | 3.959 | 241.0 | 2006 | |
| 73. | Julian Rodriguez | 3.971 | 170.0 | 2005 | |
| 74. | Timothy Lawson | 3.971 | 215.3 | 2005 | |
| 75. | Devin Bostwick | 3.985 | 221.3 | 2006 | |
| 76. | Bill Poteet | 3.988 | 187.3 | 2006 | |
| 77. | Juan McDade | 4.004 | 193.3 | 2006 | |
| 78. | Archie Aubry | 4.008 | 247.0 | 2005 | |
| 79. | Justin Munford | 4.017 | 192.7 | 2006 | |
| 80. | Tokuichirou Kenzo | 4.018 | 239.7 | 2005 | |
| 81. | Joey Leiva | 4.053 | 177.7 | 2006 | |
| 82. | Boris Aznar | 4.056 | 219.7 | 2006 | |
| 83. | Leonardo Moya | 4.058 | 173.0 | 2006 | |
| 84. | Mark Fite | 4.065 | 179.3 | 2005 | |
| 85. | Ronny Boyle | 4.073 | 256.3 | 2005 | |
| 86. | Stanley Terrell | 4.079 | 231.7 | 2005 | |
| 87. | Bill Poteet | 4.089 | 233.3 | 2005 | |
| 88. | Antonio Manrique | 4.092 | 213.3 | 2006 | |
| 89. | Jonathan Silverstein | 4.147 | 199.7 | 2006 | |
| 90. | Brian Sisemore | 4.160 | 220.7 | 2006 | |
| 91. | Sal Leyva | 4.187 | 187.0 | 2006 | |
| 92. | Sal Leyva | 4.225 | 213.0 | 2005 | |
| 93. | Alexander Deen | 4.235 | 204.0 | 2005 | |
| 94. | Lionel Slater | 4.239 | 212.3 | 2006 | |
| 95. | Julio Lozoya | 4.239 | 218.7 | 2006 | |
| 96. | Rauru Kiyonobu | 4.248 | 220.3 | 2006 | |
| 97. | Ruben Campbell | 4.254 | 194.7 | 2006 | |
| 98. | Robert Danielson | 4.257 | 222.0 | 2006 | |
| 99. | Anthony Calderon | 4.260 | 255.7 | 2005 | |
| 100. | Lionel Slater | 4.263 | 221.7 | 2005 |
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