| No. | Champion | Championship change | Reign statistics | Notes | Ref. |
| Date | Event | Location | Reign | Days |
| NWA Midwest/IWA Mid-South Women's Championship |
| 1 | Lacey | May 30, 2004 | House show | Hammond, Indiana | 1 | 110 | Defeated Mercedes Martinez and Daizee Haze in a three-way elimination match in tournament final to become the inaugural champion. | |
| 2 | Mercedes Martinez | September 17, 2004 | 2004 Ted Petty Invitational | Highland, Indiana | 1 | 120 | | |
| 3 | Ariel | January 15, 2005 | New England Championship Wrestling Live event | Framingham, Massachusetts | 1 | 28 | This was a three-way match also involving Hayley Skye. | |
| 4 | Daizee Haze | February 12, 2005 | House show | Highland, Indiana | 1 | 84 | This was a six-way elimination match also involving Cheerleader Melissa, Mickie Knuckles, MsChif and Sara Del Rey. | [3] |
| 5 | MsChif | May 7, 2005 | House show | Streamwood, Illinois | 1 | 35 | This live event was promoted by Ed Chuman. | |
| IWA Mid-South Women's Championship |
| 6 | Mickie Knuckles | June 11, 2005 | House show | Philadelphia, Pennsylvania | 1 | 160 | This was a three-way match also involving Allison Danger. On June 17, 2005, in Midlothian, Illinois, Ed Chuman, NWA Midwest promoter, declares that a supposed title change on June 11 (an IWA Mid-South event in Philadelphia, PA where Mickie Knuckles defeated MsChif and Allison Danger in a three-way match to become champion in IWA's eyes) is invalid due to the match not being sanctioned by the NWA. The two titles then split into separate entities as IWA Mid-South promoter Ian Rotten recognized Knuckles as champion with her win over MsChif. Knuckles is thus the first strictly IWA Mid-South Women's Champion, and is where that portion of the title lineage begins. | |
| 7 | Hailey Hatred | November 18, 2005 | IWA Mid-South King Of The Death Matches 2005 | Plainfield, Indiana | 1 | 82 | | [4] |
| 8 | Mickie Knuckles | February 8, 2006 | IWA East Coast A Need To Bleed 2006 | South Charleston, West Virginia | 2 | 528 | | [5] |
| 9 | Chuck Taylor | July 21, 2007 | IWA Mid-South Bad Blood Rising | Joliet, Illinois | 1 | 14 | Taylor's IWA Mid-South Heavyweight Championship was also on the line. He became the first male wrestler to hold the title. | [6] |
| 10 | Mickie Knuckles | August 4, 2007 | IWA Mid-South Extreme Heaven 2007 | Plainfield, Indiana | 3 | 272 | This was a no countouts, falls count anywhere match. | [7] |
| 11 | Daizee Haze | May 2, 2008 | IWA Mid-South Fan Appreciation Night | Indianapolis, Indiana | 2 | 218 | This was a three-way match also involving Sara Del Rey. | [8] |
| — | Vacated | December 6, 2008 | Candido Cup 2008 | Joliet, Illinois | — | — | Ian Rotten announced that all titles are being done away with in IWA except for the IWA World Heavyweight and Light Heavyweight Titles. | [9] |
| 12 | Shotzi Blackheart | April 19, 2018 | IWA Mid-South Miss Independent | Memphis, Indiana | 1 | 182 | Defeated Kikyo in the tournament final to win the reactivated title. | |
| 13 | Amazing Maria | October 18, 2018 | IWA Mid-South 22nd Anniversary Show | Jeffersonville, Indiana | 1 | 65 | This was a falls count anywhere match. | [11] |
| 14 | Lukas Jacobs | December 22, 2018 | IWA Mid-South Big Ass Christmas Bash 2018 | Jeffersonville, Indiana | 1 | 12 | Jacobs became the second male wrestler to hold the title. | [12] |
| 15 | Max The Impaler | January 3, 2019 | IWA Mid-South RassleKingdom | Jeffersonville, Indiana | 1 | 43 | | |
| 16 | Amazing Maria | February 15, 2019 | IWA Mid-South Heartbreak 2019 | Jeffersonville, Indiana | 2 | 15 | This was a three-way match also involving Thunderkitty. | |
| 17 | Nevaeh | March 2, 2019 | IWA Mid-South In Like A Lion 2019 | Jeffersonville, Indiana | 1 | 109 | | |
| 18 | Max The Impaler | May 23, 2019 | IWA Mid-South Payback, Pain & Agony 2019 | Jeffersonville, Indiana | 2 | 49 | | |
| 19 | Alice Crowley | July 11, 2019 | IWA Mid-South Welcome To The Danger Zone | Jeffersonville, Indiana | 1 | 238 | | |
| 20 | Haley J | March 5, 2020 | IWA Mid-South Let The Madness Begin | Jeffersonville, Indiana | 1 | 233 | This was a tables match. | |
| 21 | Thunderkitty | October 24, 2020 | IWA Mid-South 24th Anniversary Show: We Are IWA | Indianapolis, Indiana | 1 | 103 | | |
| 22 | Haley J | February 4, 2021 | IWA Mid-South Opportunity Knocks | Indianapolis, Indiana | 2 | 7+ | This was a four-way match also involving Malia Hosaka and Amazing Maria. | |