Before it closed in 1976, St. Mary's College was the third oldest operating Catholic college for boys in the nation and was a leader in Catholic education in the state. Established in 1821, St. Mary's was in operation thirteen years before Marion County was formed. The extant main college buildings on St, Mary's campus are of a style and composition that reflect the early character of the complex.

The Columbia, Shamrock, Old Chapel, and Refectory buildings were all constructed in the 1830s at a cost of $50,000.

Some of the well-known alumni of St. Mary's include: The Honorable J. Proctor Knott (1830-1911, later Governor of Kentucky), Theodore O'Hara (1820-1851, journalist and author) and The Honorable Elisha Standiford (President of the Louisville and Nashville Railroad from 1875 to 1880). - NRHP Statement of Significance (January 29, 1980)