The school officially opened on October 15, 1866 and was granted a charter by the Maryland General Assembly the following spring. Soon thereafter, the seminary moved into a spacious new three-story brick building on West Main Street. The new seminary building was one of the largest structures in town and consisted of lecture rooms on the first floor, sleeping quarters for the school's boarding students on the second and third floors, and sleeping quarters for school faculty in the attic level. The basement contained a large kitchen and the rear ell wing housed offices and the school's library. A cupola atop the school afforded a panoramic view of the village, South Mountain, and the surrounding Middletown Valley. ​

The German Reformed Church in Burkittsville attained sufficient membership to support its own minister in 1846. In that year, the congregation withdrew from the pastoral care of Christ Reformed Church in Middletown and called their own minister, the Rev. George Lewis Staley. Boundaries were drawn up for the new Burkittsville Charge which was centered at the church in Burkittsville and encompassed the nearby communities of Petersville, Berlin (Brunswick), and Knoxville. Even before this significant year, the congregation's ministers had traveled to Knoxville and held occasional services as early as 1840.