| Player | Team | SO |
|---|---|---|
| Shane Bieber | Kankakee | 405 |
| Jacob deGrom | Arizona | 370 |
| Lucas Giolito | Chicago | 335 |
| Gerrit Cole | Tacoma | 335 |
| Yu Darvish | Boise | 324 |
| Trevor Bauer | Ohio | 322 |
| Aaron Nola | Portland | 312 |
| Luis Castillo | Dakota | 306 |
| Brandon Woodruff | Portland | 304 |
| Dinelson Lamet | Fraser | 293 |
| Zac Gallen | Orlando | 290 |
| Carlos Carrasco | Foscoe | 271 |
| Corbin Burnes | Brooklyn | 255 |
| Framber Valdez | Foscoe | 254 |
| Kevin Gausman | Kankakee | 251 |
| Max Scherzer | Foscoe | 250 |
| Tyler Glasnow | Dakota | 239 |
| Zach Eflin | Herefordshire | 236 |
| Blake Snell | Orlando | 229 |
| Lance Lynn | Pea Ridge | 224 |