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| Career Strikeouts Leaderboard | |
| * - Indicates Hall of Fame Bold - Indicates active player |
| Rank | Player | Strikeouts | IP | Years | Single Season Leaderboard |
| 1. | David Echegaray | 5007 | 4812.6 | 2003-2026 | |
| 2. | James Yim * | 4714 | 4445.9 | 2003-2021 | |
| 3. | Steven Williams * | 4244 | 3524.0 | 2002-2017 | |
| 4. | Skip Burns | 3977 | 4027.6 | 2001-2020 | |
| 5. | Edgardo Castillo * | 3664 | 3758.6 | 2001-2018 | |
| 6. | Jose Langlois | 3614 | 3377.9 | 2004-2020 | |
| 7. | Ryan Turner * | 3608 | 3744.9 | 2001-2021 | |
| 8. | Hugh Hoots | 3229 | 3766.6 | 2002-2018 | |
| 9. | Ben Lamela | 2691 | 3342.6 | 2008-2025 | |
| 10. | Scott Bartell | 2651 | 4101.3 | 2003-2021 | |
| 11. | Dennis Morelock * | 2512 | 4013.6 | 2003-2017 | |
| 12. | Clarence McNatt * | 2484 | 2894.0 | 2003-2017 | |
| 13. | Albert Olmos | 2479 | 3489.6 | 2000-2014 | |
| 14. | Aaron Bacon * | 2426 | 3356.0 | 2000-2012 | |
| 15. | Chad Schmidt | 2380 | 3346.6 | 2015-2029 | |
| Donte Dasilva | 2380 | 3018.0 | 2003-2017 | ||
| 17. | Mark Trowers | 2371 | 3535.9 | 2010-2025 | |
| 18. | J.J. Cobb | 2345 | 3210.6 | 2000-2014 | |
| 19. | Richard San Juan | 2329 | 3143.3 | 2017-2029 | |
| 20. | Mark Torrence | 2286 | 2896.3 | 2002-2015 | |
| 21. | Ramon Cordova | 2272 | 2756.6 | 2017-2029 | |
| 22. | Alfred Marenco | 2256 | 2677.0 | 2005-2016 | |
| 23. | Ridge Thompson | 2181 | 2447.6 | 2006-2020 | |
| 24. | Jamie Agee | 2165 | 3207.3 | 2005-2021 | |
| 25. | Lucas Lara | 2164 | 2535.0 | 2004-2017 | |
| 26. | Dustin Carrasquillo | 2160 | 2135.3 | 2000-2010 | |
| 27. | Dirk Carr | 2149 | 2559.3 | 2007-2019 | |
| 28. | Malik Meng | 2128 | 2438.6 | 2000-2009 | |
| 29. | Osvaldo Pedraza | 2092 | 3311.0 | 2003-2017 | |
| 30. | Kevin Smith | 2056 | 2599.0 | 2019-2029 | |
| 31. | Joseph Smartt | 2030 | 2503.3 | 2002-2014 | |
| 32. | Xavier Josephs | 2023 | 2994.6 | 2003-2018 | |
| 33. | Dennis Wright * | 2017 | 3380.6 | 2001-2014 | |
| 34. | Paul Hall | 1987 | 2664.0 | 2018-2029 | |
| 35. | Leo Cleland * | 1986 | 2815.6 | 2004-2017 | |
| 36. | Samson Steele * | 1967 | 2596.0 | 2000-2011 | |
| 37. | James Alexander | 1962 | 2806.6 | 2011-2026 | |
| 38. | Paul Wendler | 1958 | 2332.6 | 2002-2015 | |
| 39. | Galon Thrace | 1948 | 2419.3 | 2014-2024 | |
| 40. | Ramon Quintana | 1938 | 2180.3 | 2000-2013 | |
| 41. | Eric Song | 1925 | 1659.0 | 2000-2011 | |
| 42. | Leon Collins | 1924 | 2526.3 | 2015-2027 | |
| 43. | Thomas Showers * | 1901 | 3348.0 | 2000-2013 | |
| 44. | Alfonso Arevalo | 1893 | 2110.6 | 2000-2011 | |
| 45. | Armand Banuelos | 1866 | 3088.0 | 2000-2012 | |
| 46. | Christopher Millar | 1863 | 2633.3 | 2014-2029 | |
| 47. | Higinio Delmonte | 1857 | 3025.3 | 2014-2029 | |
| 48. | Rafael Souza | 1849 | 2287.6 | 2003-2022 | |
| 49. | Todd Neary | 1842 | 2286.6 | 2019-2029 | |
| 50. | Russ Gobbler | 1841 | 2781.6 | 2016-2029 | |
| 51. | Danny Day | 1835 | 2527.6 | 2014-2026 | |
| 52. | Tobias Escobar | 1834 | 2817.9 | 2006-2019 | |
| 53. | Jeeves Vanhooten | 1817 | 3186.9 | 2000-2014 | |
| 54. | Joe O'Malley | 1816 | 2718.6 | 2003-2016 | |
| 55. | Humberto Deleon | 1812 | 3174.9 | 2014-2029 | |
| 56. | Paul Harrington | 1781 | 2099.3 | 2000-2009 | |
| 57. | Emeril Loux | 1780 | 2540.0 | 2004-2018 | |
| 58. | Abraham Grayston | 1755 | 3311.3 | 2006-2022 | |
| 59. | Ronaldo Laguna | 1750 | 2574.0 | 2017-2029 | |
| 60. | Geoff Stagner | 1747 | 2609.0 | 2011-2025 | |
| 61. | Richard Hirsh | 1742 | 3209.9 | 2000-2012 | |
| 62. | Robert Garza * | 1735 | 2458.6 | 2004-2015 | |
| 63. | Randy Kennedy | 1727 | 2598.6 | 2000-2010 | |
| 64. | Bruce Sikes | 1704 | 2269.0 | 2017-2029 | |
| 65. | Russell Hults | 1693 | 2887.3 | 2005-2020 | |
| 66. | Kelly Giuliani | 1685 | 1553.0 | 2000-2007 | |
| 67. | Roger Morrison | 1680 | 2573.6 | 2002-2013 | |
| 68. | Gregory Hart | 1675 | 2858.3 | 2000-2012 | |
| 69. | Paul Knutson | 1669 | 2506.3 | 2005-2018 | |
| 70. | Aaron Hightower | 1668 | 2198.6 | 2015-2029 | |
| 71. | Roderigo Pequero | 1663 | 2668.6 | 2018-2029 | |
| 72. | Lowell Stang * | 1662 | 2987.9 | 2007-2021 | |
| 73. | Armando Quinonez * | 1650 | 1638.6 | 2000-2007 | |
| 74. | William Roberts | 1633 | 2103.6 | 2008-2021 | |
| 75. | Max Guerra | 1625 | 2120.3 | 2008-2020 | |
| 76. | Andrew Albury | 1601 | 2407.3 | 2001-2014 | |
| 77. | Benny Suarez | 1598 | 2730.9 | 2016-2029 | |
| 78. | Jeffrey Cargo | 1596 | 2881.3 | 2000-2011 | |
| 79. | Fred Washington | 1595 | 2303.3 | 2005-2019 | |
| 80. | Glen Robinson | 1593 | 2060.6 | 2004-2018 | |
| 81. | Leonard Lubbers | 1553 | 2356.6 | 2003-2013 | |
| 82. | Joseph Seybert | 1550 | 1290.0 | 2000-2005 | |
| 83. | Rusty Skittles | 1533 | 2706.3 | 2007-2020 | |
| 84. | Alex Ramirez | 1529 | 2007.9 | 2001-2015 | |
| 85. | David Evans | 1522 | 1412.3 | 2000-2006 | |
| 86. | Xalbador Laguna | 1518 | 2146.0 | 2019-2029 | |
| Kelvin Palen | 1518 | 2641.3 | 2000-2010 | ||
| 88. | Jesus Aviles | 1505 | 1789.6 | 2003-2012 | |
| 89. | Adam Burton | 1481 | 2164.9 | 2009-2022 | |
| 90. | Benicio Andaverde | 1468 | 2653.3 | 2016-2029 | |
| 91. | William Tinoco | 1447 | 1597.3 | 2019-2029 | |
| 92. | Damien Holcombe | 1444 | 2356.6 | 2008-2019 | |
| 93. | Curtis Yoo | 1438 | 2331.9 | 2013-2027 | |
| 94. | Robert Ford | 1437 | 1994.0 | 2000-2010 | |
| 95. | Ferdinand Lueras | 1423 | 2187.3 | 2000-2010 | |
| 96. | Blaine Titsworth | 1421 | 1930.6 | 2000-2009 | |
| 97. | Huey Pearson | 1420 | 1919.3 | 2000-2011 | |
| 98. | Roberto Villagomez | 1418 | 2099.3 | 2013-2024 | |
| 99. | Randall Spates | 1416 | 2129.3 | 2006-2018 | |
| 100. | Christopher Kearns | 1414 | 2471.0 | 2000-2010 |
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