The Northwoods League has had tremendous success preparing the elite collegiate athletes across the country for the minor leagues. Thus, many former players have advanced their way to the Big Leagues. Below is a current list of NWL players that are in Major League Baseball.
| Name | Position | NWL Team | Year | Pro Affiliate | Level | League | Team | Status | Draft | Round | Year |
| Asche, Cody | INF | Duluth | 2009-10 | Philadelphia | MLB | National | Philadelphia | Active | Philadelphia | 4 | 2011 |
| Barmes, Clint | INF | Kenosha/Waterloo | 1998-99 | Pittsburgh | MLB | National | Pittsburgh | Active | Colorado | 10 | 2000 |
| Black, Victor | RHP | La Crosse | 2007 | NY Mets | MLB | National | New York | Active | Pittsburgh | 1 | 2009 |
| Brantly, Rob | C | La Crosse | 2009 | Miami | MLB | National | Miami | Active | Detroit | 3 | 2010 |
| Calhoun, Kole | OF | Eau Claire | 2007-09 | LA Angels | MLB | American | LA Angels | Active | LA Angels | 8 | 2010 |
| Craig, Allen | OF | Alexandria | 2003,05 | St. Louis | MLB | National | St. Louis | Active | St. Louis | 8 | 2006 |
| Crawford, Brandon | INF | Mankato | 2005 | San Francisco | MLB | National | San Francisco | Active | San Francisco | 4 | 2008 |
| Descalso, Daniel | INF | Wisconsin | 2006 | St. Louis | MLB | National | St. Louis | Active | St. Louis | 3 | 2007 |
| Dirks, Andy | OF | Brainerd | 2006-07 | Detroit | MLB | American | Detroit | Active | Detroit | 8 | 2008 |
| Duda, Lucas | OF | Alexandria | 2006 | NY Mets | MLB | National | New York | Active | NY Mets | 7 | 2007 |
| Ethier, Andre | OF | Rochester | 2002 | LA Dodgers | MLB | National | Los Angeles | Active | Oakland | 2 | 2003 |
| Flynn, Brian | LHP | Rochester | 2009/11 | Miami | MLB | National | Miami | Active | Detroit | 7 | 2011 |
| Gee, Dillon | RHP | Brainerd | 2005 | NY Mets | MLB | National | New York | Active | NY Mets | 21 | 2007 |
| Goins, Ryan | INF | Waterloo | 2008 | Toronto | MLB | American | Toronto | Active | Toronto | 4 | 2009 |
| Gorzelanny, Tom | LHP | St. Cloud | 2001 | Milwaukee | MLB | National | Milwaukee | Active | Pittsburgh | 2 | 2003 |
| Granderson, Curtis | OF | Mankato | 2001 | NY Yankees | MLB | American | New York | Active | Detroit | 3 | 2002 |
| Halton, Sean | INF | Mankato | 2006 | Milwaukee | MLB | National | Milwaukee | Active | Milwaukee | 13 | 2009 |
| Hannahan, Jack | INF | Mankato | 1999 | Cincinnati | MLB | National | Cincinnati | Active | Detroit | 3 | 2001 |
| Holaday, Bryan | C | Alexandria | 2008 | Detroit | MLB | American | Detroit | Active | Detroit | 6 | 2010 |
| Hundley, Nick | C | Alexandria | 2004 | San Diego | MLB | National | San Diego | Active | San Diego | 2 | 2005 |
| Janssen, Casey | RHP | Wisconsin | 2000-01 | Toronto | MLB | American | Toronto | Active | Toronto | 4 | 2004 |
| Jennings, Dan | LHP | Waterloo | 2006-07 | Miami | MLB | National | Miami | Active | Florida | 9 | 2008 |
| Johnson, Erik | RHP | Alexandria | 2009 | Chicago WS | MLB | American | Chicago WS | Active | Chicago WS | 2 | 2011 |
| Kieschnick, Roger | OF | St. Cloud | 2006 | San Francisco | MLB | National | Giants | Active | San Francisco | 3 | 2008 |
| LeCure, Sam | RHP | Brainerd | 2005 | Cincinnati | MLB | National | Cincinnati | Active | Cincinnati | 4 | 2005 |
| Melancon, Mark | RHP | Duluth | 2004 | Pittsburgh | MLB | National | Pittsburgh | Active | NY Yankees | 9 | 2006 |
| Neshek, Pat | RHP | Wisconsin | 2000 | Oakland | MLB | American | Oakland | Active | Minnesota | 6 | 2002 |
| Pacheco, Jordan | INF | La Crosse | 2005 | Colorado | MLB | National | Colorado | Active | Colorado | 12 | 2007 |
| Pagnozzi, Matt | C | Madison | 2002 | Houston | MLB | American | Houston | Active | St. Louis | 8 | 2003 |
| Petricka, Jacob | RHP | Mankato | 2009 | Chicago WS | MLB | American | Chicago | Active | Chicago WS | 2 | 2010 |
| Pierre, Juan | OF | Manitowoc | 1996 | Miami | MLB | National | Miami | Active | Colorado | 13 | 1998 |
| Pillar, Kevin | OF | Wisconsin | 2010 | Toronto | MLB | American | Toronto | Active | Toronto | 32 | 2011 |
| Reed, Evan | RHP | Waterloo | 2005 | Detroit | MLB | American | Detroit | Active | Texas | 3 | 2007 |
| Reynolds, Matt | LHP | Rochester | 2006 | Arizona | MLB | National | Arizona | Active | Colorado | 20 | 2007 |
| Rodriguez, Fernando | RHP | Duluth | 2003 | Houston | MLB | American | Houston | Active | LA Angels | 18 | 2003 |
| Ruf, Darin | INF | Wisconsin | 2007 | Philadelphia | MLB | National | Philadelphia | Active | Philadelphia | 20 | 2009 |
| Sale, Chris | LHP | La Crosse | 2008 | Chicago WS | MLB | American | Chicago | Active | Chicago WS | 1 | 2010 |
| Sanchez, Tony | C | Battle Creek | 2007 | Pittsburgh | MLB | National | Pittsburgh | Active | Pittsburgh | 1 | 2009 |
| Scherzer, Max | RHP | La Crosse | 2004 | Detroit | MLB | American | Detroit | Active | Arizona | 1 | 2006 |
| Semien, Marcus | INF | Alexandria | 2009-10 | Chicago WS | MLB | American | Chicago WS | Active | Chicago WS | 6 | 2011 |
| Smyly, Drew | LHP | Duluth | 2009 | Detroit | MLB | American | Detroit | Active | Detroit | 2 | 2010 |
| Straily, Dan | RHP | St. Cloud | 2009 | Oakland | MLB | American | Oakland | Active | Oakland | 24 | 2009 |
| Wagner, Neil | RHP | Mankato | 2004-05 | Toronto | MLB | American | Toronto | Active | Cleveland | 21 | 2005 |
| Walters, Zach | INF | Duluth | 2009 | Washington | MLB | National | Washington | Active | Arizona | 9 | 2010 |
| Willingham, Josh | OF | Austin | 1998-99 | Minnesota | MLB | American | Minnesota | Active | Florida | 17 | 2000 |
| Worth, Danny | INF | Alexandria | 2006 | Detroit | MLB | American | Detroit | Active | Detroit | 2 | 2007 |
| Zimmermann, Jordan | RHP | Eau Claire | 2006 | Washington | MLB | National | Washington | Active | Washington | 2 | 2007 |
| Zobrist, Ben | OF | Wisconsin | 2003 | Tampa Bay | MLB | American | Tampa Bay | Active | Houston | 6 | 2004 |