Charter members included Armstrong State (later Armstrong Atlantic State University and now merged into Georgia Southern University) (1983–1987), Augusta (later Augusta State University and now merged into Augusta University) (1983–1990), Campbell University (1983–1994; 2011–present), Baptist College (now Charleston Southern University) (1983–present), Coastal Carolina University (1983–2016), Radford University (1983–present) and Winthrop University (1983–present).
The expansion of membership occurred during the 1980s and '90s. Some of those members are the University of North Carolina at Asheville (1984–present), Davidson College (1990–1992), Liberty University (1991–2018), the University of Maryland, Baltimore County (1992–1998), the University of North Carolina at Greensboro (1992–1997), Towson University (1992–1995), Elon University (1999–2003), High Point University (1999–present) and Birmingham–Southern College (2000–2006).
The Big South Conference began sponsoring football in 2002, with Charleston Southern, Elon (at the time) and Liberty (Gardner–Webb University also joined as a football-only member) fielding teams; Coastal Carolina and Virginia Military Institute (VMI) joined the conference as football-only members in 2003. In that same athletic year, VMI also joined the conference for all sports, but left to re-join the Southern Conference in 2014. Presbyterian College joined the conference in 2007, moving up from Division II, and became eligible for regular-season championships and conference honors during the 2008–09 athletic year. Gardner–Webb, which had been a football-only member since 2002, joined the conference for all sports on July 1, 2008. Campbell rejoined the Big South for all sports except football in the 2011–12 athletic year. Longwood University accepted an invitation to join the Big South on January 23, 2012, and membership formally began July 1 of that year; Longwood had been independent since 2004, during their transition to Division I. In 2014, following the departure of VMI, the conference returned to a single-division structure. On September 1, 2015, Coastal Carolina announced they would leave the conference following the 2015–16 school year to transition to and the Sun Belt Conference. On June 30, 2016, the day before the school joined the Sun Belt, Coastal Carolina won the 2016 College World Series in baseball. This was the first time in conference history that a team won an NCAA championship in any sport.
In September 2016, the Big South and the Atlantic Sun Conference (ASUN) announced a football partnership that effectively combined the two conferences in that sport. Under its terms, any members of either conference that add or upgrade to scholarship football, provided they fall within the current geographic footprint of the two leagues, automatically join Big South football. At the time of announcement, the only ASUN member that played scholarship football, Kennesaw State, was already a Big South football member. The partnership also provides a guaranteed football home to the leagues' non-scholarship football programs (at that time, Campbell from the Big South, and Jacksonville and Stetson from the ASUN) should they upgrade to scholarship status.
In November 2016, Campbell announced that it would begin offering scholarships and move its football program from the to the Big South in 2018.
In December 2016, the University of North Alabama, ASUN, and the Big South Conference announced that, effective in 2018, the school will leave the Division II Gulf South Conference and will join ASUN in non-football sports and the Big South in football. UNA has won three Division II NCAA national championships in football and has won at least a share of the Gulf South Conference football championship for four consecutive seasons through 2016.
Three months later, Liberty announced that it would begin a transition to FBS football in July 2017 and leave the Big South football league in 2018. Liberty and the Big South agreed later in 2017 that the school would continue to house all of its non-football sports (except for field hockey and women's swimming, neither of which is sponsored by the Big South) in that conference for the immediate future. Once Liberty became a full FBS member at the start of the 2019–20 school year, it would have technically become a Big South associate member (barring the school joining an FBS conference). However, Liberty's plans would change several months later, as it instead announced in May 2018 that it would move its non-football sports to the ASUN effective that July (except for the aforementioned field hockey and women's swimming, also not sponsored by the ASUN).
In November 2017, the University of South Carolina Upstate and Hampton University announced that they would be leaving the ASUN and Mid-Eastern Athletic Conference, respectively, to join the Big South, starting in the fall of 2018.
On November 19, 2017, Presbyterian College announced that it would be moving its football program to the non-scholarship Pioneer Football League. Presbyterian's last Big South football season will be 2019; the Blue Hose plan to play the 2020 season as an independent before joining the Pioneer League for 2021 and beyond. The Blue Hose will remain a member of the Big South in all other sports.