St. Vincent’s College and Seminary was founded in 1838 and was responsible for the education of thousands of students, especially young men aspiring to the priesthood. The cornerstone of the first building of the Seminary was laid in spring 1843. In 1871, a three-story west wing was added to provide dormitory space and to create a large chapel and lecture room. near the Seminary grounds, and a tornado in 1850 which damaged main buildings and the Civil War.

Declining enrollments in the 1890s nearly forced the closing of the college. Around 1910, however, the role of the school was redefined, and it became a type of preparatory school for the priesthood. Relatively healthy enrollments of 70 to 80 students became the norm. Young students at the college seemed to integrate increasingly into the local culture in the 1950s and years following, particularly as participants in sports activities. Eventually, dwindling enrollment forced the province to close the school in 1979. When the high school closed, St. Vincent's College was changed from a preparatory seminary to a center for evangelization. The Evangelization Center hosted retreats and other religious activities until 1989. The property was sold to Southeast Missouri State University in 1998.

The property acquired by Southeast in 1998 included 60,000 square feet of existing interior building space and 16.6 acres of real estate. Eventually, the University and the City of Cape Girardeau came together in a joint partnership to provide public and private funding for the new facility which would be home to a newly-created School of Visual and Performing Arts, comprised of the academic departments of Art, Music, and Theatre/Dance. Also included were plans to bring the University Museum into the River Campus complex.

Work on the Seminary, including landscaping was completed by the end of April, 2007. The move of faculty offices of the Departments of Art, Music, and Theatre/Dance was completed mid-summer, 2007. Fall classes began in the Seminary Building Aug. 20, 2007.