Salem Academy was founded four years before the Declaration of Independence was signed, and has not closed its doors in more than 200 years. Salem Academy is the oldest continuously operating educational institution for girls and women in the United States.

The Moravians, an early Protestant denomination, established the village of Salem in 1766. Among the town's early residents were sixteen girls and women who traveled more than 500 miles from Bethlehem, Pennsylvania, to join the new community. Believing that women deserved an education comparable to that given to men—a radical view for that era—the Moravians began a school for girls in 1772, and Elisabeth Oesterlein was the first teacher.

Within less than two decades of its founding, the reputation of the school for girls had spread throughout the South. By the turn of the nineteenth century, the school had begun to accept boarding students, and in 1805, South Hall on Salem Square was constructed to provide additional dormitory rooms.

By the middle of the nineteenth century, the Academy had expanded threefold: The 1805 building had been enlarged, the Inspector's House (the residence and office of the principal) had been built and expanded, and the Gemein Haus (congregation house) had been renovated and given over entirely to the school. In 1856 the students and faculty of the Academy moved into the newly constructed Main Hall, and in 1888, Annex Hall was built to house additional students.

During the 1860s, college-level courses were added to the curriculum. Reflecting changes in its character and mission, the institution's name was officially changed in 1907 to Salem Academy and College. Less than thirty years later, a new and wholly separate set of facilities for the Academy was built on the eastern perimeter of the campus, and the existing buildings on Salem Square were given over to the College. From modest beginnings, Salem has evolved into a girls' preparatory school of national standing and a women's college of genuine distinction.