The College opened as an educational institution in September 1837, to day students and boarders, offering second level education in the humanities, with a limited contribution from the sciences, to students wishing to prepare for priesthood as well as careers in business and other professions.
In 1842 Archbishop of Cashel Michael Slattery established a foreign mission department in St. Patrick's College, Thurles, many of its graduates going to the United States, Australia and New Zealand.