At age 18, Byrne entered St. Thomas Seminary in Bardstown, Kentucky, to begin his preparatory studies for the priesthood.After a few years at Bardstown, Byrne continued his classical education at Mount St. Mary's Seminary of the West in Cincinnati, graduating in 1865. He attended the seminary alongside Peter Fenelon Collier, whom Byrne befriended and dissuaded from entering the priesthood. He helped Collier obtain a position at Sadlier, launching a successful publishing career.
