The conference was founded in 1975 as the Virginia College Conference. On January 1, 1976, the name was changed to the Old Dominion Athletic Conference. The 1976–77 season was the first in which championships were offered. In 1982–83, women's sports were added. In 1988, Virginia Wesleyan was added as a member, and, in 1990, Guilford became the first member located outside Virginia. Catholic University was a full-sport member in the 1980s along with Maryville College. Both resigned their memberships in the mid-to-late 1980s. In 1999, Catholic returned as a football-only member. The only other school that has left the conference is Mary Baldwin College, which left in 1999 to join the Atlantic Women's Colleges Conference.
In 2010 the ODAC announced the addition of Shenandoah University to its full-time membership, with its first full year of involvement during the 2012-13 academic year.
The league office moved its physical location from Salem, Virginia, to Forest, Virginia, just outside of centrally located Lynchburg, and contracted with Jim Ward Design for its new marks.
The conference hosts the Division III championships in football and men's basketball, both of which are held in Salem, Virginia. DIII softball has called Salem home along with Division III women's lacrosse and volleyball. Since 1993 - the conference and city have hosted over 50 Division III National Championships.
^The Middle Atlantic Conferences have a total of 18 members. However, the MAC operates as three separate groups under one administrative structure—the Commonwealth Conference, Freedom Conference, and the Middle Atlantic Conference. The last of these is generally used to form a single conference in sports that have only a few MAC members participating; the only sport operated by this group with more than 11 participating schools is cross-country for both men and women, in which 17 of the 18 total members participate.