Punk's home promotion for his early career is usually considered to be Independent Wrestling Association: Mid-South (IWA:Mid-South). During Punk's time in IWA:Mid-South, he had high profile feuds with Colt Cabana and Chris Hero while also rising to the top of the roster winning the IWA Mid-South Light Heavyweight Championship twice and the IWA Mid-South Heavyweight Championship on five separate occasions, beating stars like A.J. Styles, Cabana and even Eddie Guerrero for that Championship. Punk's feud with Hero included a 55-minute TLC match, a 93-minute two out of three falls match, and several 60-minute time limit draws.
Punk's matches with Cabana led him to being hired by the Ring of Honor promotion. From February 2003 until May 2004, Punk refused to wrestle for IWA:Mid-South, because he claims that this was in protest to Ian Rotten's mistreatment of Chris Hero in the company. Hero, however, has stated he believes there were other reasons, and Rotten's treatment of him was just an excuse by Punk to stop working for the company. Eventually Punk returned to IWA:Mid-South and continued to perform as a wrestler and commentator for them until 2005 when he was signed to World Wrestling Entertainment. His last appearance in IWA:Mid-South was on July 2, 2005 in which he competed in a 60-minute time limit draw against Delirious.