St. Andrews Presbyterian College traces its establishment to 1896 when Flora Macdonald College was founded at Red Springs, North Carolina. In 1958 Flora Macdonald College and Presbyterian Junior College (which was established in 1928) were merged to form St. Andrews Presbyterian College.

In the early 1950s, Presbyterians of North Carolina obtained a grant from the Ford Foundation to survey higher education in the Synod of North Carolina. As a result of that study, the Synod decided in 1955 to create a merged college at a new site.

The founders had the foresight to make a commitment to work toward breaking down the physical barriers which made it difficult for students with physical disabilities to pursue a college education. Therefore, the new campus was constructed to be accessible, with wide doorways and hallways, ramps, curb cuts, elevators and special restroom modifications. Another grant enabled the Synod to plan a new college of high academic quality and Christian purpose, one with contemporary style and design.