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.
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 also advanced a large sum to the Jesuits to maintain a seminary in Galway, in which town he built himself a residence three stories high.
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.