The seminary, chapel, and five other buildings were added to the National Register of Historic Places in 1979.

[1] The first buildings on the site of Saint Charles Seminary were the former buildings of the Emlen Institution, a boarding school for African-American and Native American youth funded from a bequest from Samuel Powers Emlen Jr., a Quaker.

[3][4] The Missionaries of the Precious Blood had arrived in Ohio in 1844 to begin serving German-speaking settlers living there.

In 1861 they purchased 200 acres of land and the former Emlen Institute to serve as a seminary for the candidates to their religious congregation, which they then placed under the patronage of St. Charles Borromeo.

The chapel was built by the sons of Ohio steepled-church designer Anton De Curtins.