[1] The school was founded after the Eastern Seventh Day Baptist Association decided to build an academy in the city of Salem.

The state granted a permit in December 1888 to build what was called the Academy of Salem, specifying that the institution was subject to the regulations and decisions of the Society of Seventh Day Baptist Education.

In 1989, Salem formed an alliance with Teikyo University in Tokyo, Japan, which changed the focus of the school to one of education of international students.

[5] Nearly 200 freshmen from Japan enrolled in the college as part of an experiment by Japanese educators to teach the 145 boys and 45 girls how to speak fluent English, experience American culture firsthand and to acquire a valuable American college degree.

[2] The Salem College Administration Building was listed on the National Register of Historic Places in 1989.

Historical documents and the original bell from the building were found in that demolition and are now housed in Salem's Benedum Library.

The institution has been exploring alternate Division II conference membership options beginning with the 2016–17 season.”[10] As of the 2023–24 school year, Salem remains an independent NCAA Division II institution with no conference affiliation in most sports, with the exception being men's and women's water polo that compete in the Western Water Polo Association.

However, Salem University and the Mountain East Conference reached a non-conference scheduling agreement for men's and women's basketball, men's and women's soccer, volleyball, baseball, and softball beginning in August of 2023 in the wake of the sudden closure of then Mountain East member Alderson Broaddus University.