Born in Carrick-on-Suir, County Tipperary O'Brien became a Home Ruler nationalist and an anti-liberal ultramontanist fashioned after Pope Pius IX.
At the age of two when his father died his mother sold the family grocery business and they moved to Limerick.
He was educated locally at St. Marys in Limerick, and at Knockbeg college, Carlow.
He studied for the priesthood in Maynooth College graduating with distinction, he was ordained then in 1839.
O'Brien was president of Saint Mary's College, in Halifax, Nova Scotia, Canada from 1840–45.