On June 9, 2001, CM Punk defeated Mark Wolf for the IWA Mid-South Light Heavyweight title in Charlestown; IN. He defeated Tarek the Great for the IWA Mid-South Light Heavyweight title on November 3, 2001. On December 5, 2001, CM Punk pinned Chris Hero in Indianapolis, IN to capture the IWA Mid-South World Heavyweight title.

On December 15, 2001, CM Punk downed "Classic" Colt Cabana in an 8-man tournament final to win the vacant MAW (Mid American Wrestling) World Heavyweight title in Wind Lake, WI. Harley Race was the special referee. Punk defeated Eddy Guerrero on March 2, 2003 in Morris, IL for the IWA Mid-South World Heavyweight title.

On December 14, 2002, CM Punk beat BJ Whitmer for the IWA Mid-South World Heavyweight title. On April 24, 2004 in Chicago, IL, CM Punk and Colt Cabana defeated The Briscoe’s to capture the ROH Tag Team title. Punk battled ROH champion Samoa Joe to a 60-minute time limit draw on October 16, 2004 in Chicago, IL. In June 2005, Punk signed with World Wrestling Entertainment. On June 18, 2005 in Morristown, NJ, he defeated Austin Aries to capture the ROH (Ring of Honor) title.

On November 9, 2005 in Louisville, KY, CM Punk pinned Ken Doane for the OVW (Ohio Valley Wrestling) Television title. CM Punk and Bryan Danielson defeated Jimmy Rave and Adam Pearce on February 11, 2006 in Lake Grove, NY. On May 3, 2006, CM Punk defeated Brent Albright (Gunner Scott) to capture the OVW title. In his ECW debut, he defeated Steve Richards on June 24, 2006 in Philadelphia, PA. On July 28, 2006, CM Punk and Seth Sky fire defeated Da Beast and The Neighborhood to capture the OVW Southern Tag Team title.