Educated in theology by the Jesuits and at the Sorbonne, Bérulle was ordained in 1599. In 1604 he went to Spain. He returned with seven nuns who established the reformed Order of the Discalced Carmelites in France.

As a result of his interest in the clerical reforms that had been proposed by the Council of Trent (1545–63), Bérulle founded the French Oratory (1611), modeled after but independent of the Oratory of St. Philip Neri. The Oratorians, a congregation of priests with no binding vows, founded new seminaries, improved preaching, promoted theological studies, and ultimately caused a general revival of the French clergy. Bérulle's Oratory served as a model for those new congregations of priests that characterize the religious history of 17th-century France—the Lazarists, the Sulpicians, and the Eudists. He exercised a decisive influence on the religious development of the Abbé de Saint-Cyran and so, through him, on Port-Royal, the centre of Jansenism and of literary activity in 17th-century France.

Bérulle unsuccessfully opposed the Cardinal de Richelieu, Louis XIII's minister, and his anti-Spanish policy. He expressed his personal spirituality in a series of devotional writings, the best known of which is the Discours de l'état et des grandeurs de Jésus (1623; “Discourse on the State and Greatnesses of Jesus”). His interest in meditation and prayer also found its way into his educational policies and became a major part of the clerical reform.