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| Second Basemen Career Strikeouts Leaderboard | |
| * - Indicates Hall of Fame Bold - Indicates active player |
| Rank | Player | Strikeouts | PA | Years | Single Season Leaderboard |
| 1. | Larry Doyle | 677 | 6994 | 1909-1922 | |
| 2. | Amby McConnell | 571 | 8500 | 1908-1923 | |
| 3. | Clyde Engle | 570 | 3913 | 1909-1920 | |
| 4. | Heinie Groh | 546 | 6878 | 1912-1929 | |
| 5. | Erve Beck | 530 | 6635 | 1901-1913 | |
| 6. | Del Pratt | 503 | 7838 | 1912-1924 | |
| 7. | George Scales | 491 | 5077 | 1920-1929 | |
| 8. | Nap Lajoie * | 443 | 7574 | 1901-1913 | |
| 9. | Jimmy Williams * | 425 | 9454 | 1901-1915 | |
| 10. | Sparky Adams | 405 | 3778 | 1922-1929 | |
| 11. | Tillie Shafer | 399 | 3198 | 1914-1925 | |
| 12. | Lefty Davis | 371 | 4861 | 1901-1911 | |
| 13. | Tom Jones | 365 | 4233 | 1907-1914 | |
| 14. | Frank O'Rourke | 363 | 7820 | 1914-1928 | |
| 15. | Bill Sweeney | 353 | 8310 | 1907-1921 | |
| 16. | George Kelly | 350 | 3133 | 1916-1926 | |
| 17. | Miller Huggins | 344 | 4144 | 1904-1915 | |
| 18. | Larry Hoffman | 339 | 7031 | 1901-1915 | |
| 19. | Gene Paulette | 336 | 4173 | 1914-1926 | |
| 20. | Rogers Hornsby | 335 | 8145 | 1915-1929 | |
| 21. | Gene Demontreville | 334 | 6048 | 1901-1912 | |
| 22. | Ivy Olson | 324 | 2079 | 1911-1919 | |
| 23. | Jay Kirke | 318 | 4446 | 1913-1924 | |
| 24. | John Leary | 293 | 2590 | 1915-1925 | |
| 25. | Bingo Demoss | 290 | 4286 | 1918-1926 | |
| 26. | Dave Brain | 287 | 4237 | 1901-1910 | |
| 27. | Cupid Childs | 279 | 1912 | 1901-1904 | |
| 28. | Roy Grimes | 278 | 3598 | 1922-1929 | |
| 29. | Lee Magee | 276 | 7727 | 1911-1925 | |
| 30. | Danny Murphy | 272 | 5528 | 1901-1912 | |
| 31. | Frank Laporte | 268 | 5690 | 1907-1918 | |
| 32. | Jimmie Dykes | 263 | 2970 | 1919-1929 | |
| 33. | Marty McManus | 242 | 4679 | 1920-1929 | |
| Sam Mertes | 242 | 3954 | 1901-1908 | ||
| 35. | Max Bishop | 240 | 3336 | 1924-1929 | |
| 36. | Jack Mills | 232 | 2141 | 1914-1924 | |
| 37. | Ossie Vitt | 223 | 5643 | 1915-1926 | |
| 38. | Jesse Baker | 222 | 3663 | 1919-1929 | |
| 39. | Art Griggs | 205 | 2332 | 1909-1919 | |
| 40. | Bill O'Neill | 199 | 3655 | 1905-1913 | |
| 41. | Johnny Rawlings | 196 | 5672 | 1915-1929 | |
| 42. | John Godwin | 191 | 3875 | 1906-1913 | |
| 43. | Tony Lazzeri | 189 | 2267 | 1926-1929 | |
| 44. | Marty Kavanagh | 188 | 3316 | 1916-1926 | |
| 45. | John Monroe | 186 | 3253 | 1921-1929 | |
| Jackie Tavener | 186 | 2701 | 1924-1929 | ||
| 47. | Peaches Graham | 185 | 793 | 1910-1914 | |
| 48. | Morrie Rath | 179 | 3491 | 1911-1922 | |
| 49. | Charlie Malay | 171 | 3471 | 1906-1917 | |
| 50. | Riggs Stephenson | 170 | 4545 | 1921-1929 | |
| Frankie Frisch | 170 | 4216 | 1919-1928 | ||
| 52. | Charlie Gehringer | 169 | 3255 | 1924-1929 | |
| 53. | Marty Berghammer | 160 | 1632 | 1916-1920 | |
| 54. | Bert Conn | 158 | 3564 | 1901-1914 | |
| Jack Morrissey | 158 | 2058 | 1902-1910 | ||
| 56. | Joe Gedeon | 155 | 4635 | 1919-1929 | |
| 57. | Bobby Lowe | 153 | 1400 | 1901-1903 | |
| 58. | Charlie Hollocher | 150 | 5276 | 1918-1929 | |
| John Jenkins | 150 | 2633 | 1922-1929 | ||
| 60. | Paddy Baumann | 140 | 1509 | 1912-1920 | |
| 61. | Dusty Miller | 137 | 2627 | 1902-1915 | |
| 62. | Bucky Harris | 125 | 5068 | 1919-1929 | |
| 63. | Cotton Tierney | 123 | 1875 | 1920-1929 | |
| John Hummel | 123 | 2366 | 1910-1919 | ||
| 65. | John Farrell | 118 | 3627 | 1901-1911 | |
| 66. | Lee Tannehill | 107 | 2279 | 1905-1914 | |
| 67. | Whitey Witt | 102 | 4363 | 1919-1927 | |
| Pete Childs | 102 | 2680 | 1901-1908 | ||
| 69. | Sam Bohne | 98 | 2233 | 1922-1929 | |
| 70. | Wally Gerber | 92 | 1272 | 1917-1921 | |
| 71. | Joe Dolan | 90 | 1029 | 1901-1909 | |
| 72. | Lloyd Christenbury | 88 | 2636 | 1919-1926 | |
| Bruno Betzel | 88 | 652 | 1920-1923 | ||
| 74. | Walter Barbare | 87 | 3590 | 1915-1927 | |
| 75. | Jack Lewis | 85 | 505 | 1912-1912 | |
| 76. | Guy Tutwiler | 82 | 775 | 1916-1924 | |
| 77. | Benny Bowcock | 80 | 1627 | 1903-1912 | |
| 78. | Luis Castro | 77 | 1895 | 1902-1907 | |
| 79. | Ethan Allen | 76 | 1322 | 1927-1929 | |
| Mike Donovan | 76 | 1012 | 1908-1915 | ||
| 81. | Ossie Bluege | 67 | 703 | 1923-1926 | |
| 82. | Kid Gleason | 65 | 1229 | 1901-1904 | |
| 83. | Ralph Young | 64 | 1190 | 1913-1922 | |
| 84. | Roy Hartzell | 62 | 713 | 1908-1918 | |
| 85. | Frank Warfield | 61 | 2496 | 1926-1929 | |
| 86. | Jim Viox | 59 | 1026 | 1916-1922 | |
| 87. | Mike McCormick | 56 | 1056 | 1909-1911 | |
| 88. | Heinie Scheer | 55 | 789 | 1925-1929 | |
| 89. | Chink Heileman | 54 | 839 | 1901-1905 | |
| 90. | Dutch Jordan | 51 | 1206 | 1903-1910 | |
| 91. | Jack Rothrock | 49 | 579 | 1925-1929 | |
| 92. | Buddy Myer | 48 | 2080 | 1925-1929 | |
| 93. | Jack Burns | 47 | 1120 | 1904-1913 | |
| 94. | Tom Daly | 41 | 611 | 1901-1902 | |
| 95. | Dick Egan | 40 | 454 | 1915-1916 | |
| 96. | Carl Lind | 37 | 697 | 1928-1929 | |
| 97. | Andy Cohen | 34 | 677 | 1927-1929 | |
| 98. | Johnny Hodapp | 30 | 1115 | 1925-1929 | |
| Lee Demontreville | 30 | 412 | 1903-1904 | ||
| 100. | Bill Fox | 29 | 449 | 1901-1905 |
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