After a failed attempt to open the school in Frederick, Maryland, and another in Harrisburg, Pennsylvania, the school opened in Carlisle, Pennsylvania, on the campus of Dickinson College on March 11, 1825, with a class of five students.

[1] In 1836–37, the seminary moved again to Mercersburg, Pennsylvania under the charter of Marshall College.

Here the work of such celebrated professors as John Williamson Nevin, Friederich Augustus Rauch, and Philip Schaff gave rise to the Mercersburg theology, noted for its historic concerns for worship, sacraments, and Church in its ecumenical expressions.

While viewed as a temporary arrangement, the present site of the seminary was not purchased until 1893.

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