Though it thrived in its early years, the Civil War took a great toll and by 1870 there were only six students enrolled, and as few as one professor at times, requiring classes to be taught by the faculty of Centre College.

In 1893, a seminary opened in Louisville, operating out of Sunday School rooms in Second Presbyterian Church at Second and Broadway, with 31 students and six professors initially, and an endowment of $104,000.

Grant died in 1901 and left his entire $300,000 estate to the seminary, which helped finance the construction of a new Gothic-style Campus.

Because of the merger, it was the only institution supported simultaneously by the northern and southern branches of the modern Presbyterian Church (USA).

Pomerville began his tenure on July 1, 2023, and was formally confirmed by the 226th General Assembly of the Presbyterian Church (U.S.A.) (PCUSA) in 2024.