John de Burgh was ordained a priest and returned to Ireland around 1624, working for two years in the Diocese of Tuam under Boetius Egan.
During the projected Plantation of Connacht in the 1630s, his influence on Catholic members of the 1634 Parliament was so great that Lord Stafford issued warrants for his arrest, necessitating de Burgh hiding until the Viceroy's recall.
He subscribed to the ordinances agreed upon for the war against Parliament, spending almost all of his time in Kilkenny assisting the seventy-two-year-old David Rothe.
Upon the death of Malachias O'Queely, he was appointed Archbishop of Tuam by the Supreme Council of the Catholic Confederation of Ireland on 11 March 1647.
He came into conflict with Walter Lynch, Vicar-capitular of Tuam, who was the Papal Nuncio's choice for the vacant see of Clonfert; however, de Burgh wanted it for his brother, Hugh.