Conference USA was formed in 1995 by merging teams from two conferences - the Great Midwest Conference and the Metro Conference - that did not sponsor Division I football. Ironically, football, as a conference sport, was instituted in 1996.

The twelve charter members were Charlotte, Cincinnati, DePaul, Houston, Louisville, Marquette, Memphis, Saint Louis, Southern Mississippi, Tulane, Alabama-Birmingham (UAB) and South Florida (USF). All, but Houston, began athletic participation in 1995. Houston joined competition in the fall of 1996 after fulfilling an obligation to complete its membership with the Southwest Conference. However, three teams were left out of the merger: Dayton, Virginia Commonwealth, and Virginia Tech.

East Carolina was admitted in 1996 as a football-only school and began competition in 1997.

Army would join in 1997 also as a football-only school and would hold that status for the rest of its membership in Conference USA. It began competing in 1998.

Texas Christian, along with East Carolina, were added in 1999 for all-sport competition and began competing in 2001.

Marquette would continue to compete in this conference until 2005-06, when it joined the Big East. Joining Marquette's departure that season were fellow conference members Cincinnati, DePaul, Louisville, and USF. Meanwhile, Charlotte and St. Louis left for the Atlantic 10; Texas Christian joined the Mountain West; and Army, a football-only C-USA member, selected to become independent again in football.

To replace the departing members, the conference enlisted Central Florida (football in the MAC and the rest of the sports in the Atlantic Sun) and Marshall from the Mid-Atlantic Conference; Rice, Southern Methodist, Tulsa, and later Texas El-Paso from the Western Athletic Conference.

Currently, the conference also has soccer-only members for men - Florida International (Sun Belt), Kentucky and South Carolina (SEC) - and women, Colorado College (a Division III school with women's soccer as a Division I sport).

Mike Slive, the Great Midwest Conference's only commissioner, was also Conference USA's first commissioner. He would be succeeded in 2002 by Britton Banowsky, who is still serving as the conference's commissioner.

The conference began in 1995 with three divisions that matched its namesake: Red, White, and Blue. In 1997, the divisions were reconstituted to form only two divisions: American and National.

• In 2003, the conference eliminated the divisions altogether.

• 1995-96: Cincinnati and Memphis
• 1996-97: Cincinnati
• 1997-98: Cincinnati
• 1998-99: Cincinnati
• 1999-00: Cincinnati
• 2000-01: Cincinnati and Southern Mississippi
• 2001-02: Cincinnati
• 2002-03: Marquette
• 2003-04: Charlotte, Cincinnati, DePaul, Memphis, and UAB
• 2004-05: Louisville
• 2005-06: Memphis
• 2006-07: Memphis
• 2007-08: Memphis