Gerson studied at the University of Paris under the noted theologian Pierre d'Ailly (Ailly, Pierre d'), later his colleague at the Council of Constance, and was elected to succeed d'Ailly as chancellor of the university in 1395.

The major theological controversy of the times, the role of the papacy in the church, was a result of the Great Schism (begun 1378), in which two rival candidates disputed the papal throne. At first, Gerson's attitude was moderate; he favoured limited reforms, opposed the convocation of a church council to depose the competing popes, and, in 1398, disapproved of the withdrawal of obedience from Benedict XIII (Benedict (XIII)), an antipope. He was gradually won over to the need for action, however, advocating and participating in the Council of Pisa (1409), at which both reigning popes, Benedict XIII and Gregory XII, were deposed and Alexander V was elected to the papacy. Since neither Benedict nor Gregory acknowledged the council's authority, there were, in effect, three popes simultaneously attempting to run the church.

In 1414 Gerson and d'Ailly led the reformers into a second council, at Constance (Constance, Council of). Under their direction, the council removed Pope John XXIII, who had succeeded Alexander V. Under pressure, Gregory XII also resigned and, finally, in 1417, Benedict XIII acceded to the council. The church was then united under Martin V. The Council of Constance also condemned the Bohemian reformer Jan Hus for heresy. Gerson opposed the theologian Jean Petit—who defended as justifiable tyrannicide the assassination (Nov. 23, 1407) of Louis, duc d'Orléans, by partisans of John the Fearless of Burgundy—but the council refused to condemn him explicitly. When Gerson left Constance (1418), he was prevented from returning to France by John and went into exile in Germany. On John's death (1419), he returned to France and settled at Lyon.

In his writings, Gerson defended the council's actions, putting forth the position that Christ had instituted the primacy of the church as the collection of the faithful, with the pope as its deputy. As such, the pope could be removed without his consent by a council of the faithful. His treatise De potestate ecclesiae (“On Ecclesiastical Power”), written between 1391 and 1415, pictured the pope as a constitutional monarch and contended that the council had merely restored the papacy to its proper role.

As a religious educator, Gerson established a curriculum based on older mystical theologies, using the teachings of St. Bonaventure as a model. To Gerson, the soul did not merely attain a union with God in prayer; soul and God became identical. In his study De theologia mystica (“On Mystical Theology”), he contrasted the mystical approach to God and religion with that of scholasticism, which emphasized study of the Bible and church history, relying on reason to achieve faith. Christian mystics should find the evidence of God in their hearts, Gerson argued, believing that love would reach further than reason and that the mystic approach was intrinsically more self-fulfilling. The Imitation of Christ, a celebrated devotional work traditionally ascribed to Thomas à Kempis, has been considered by some scholars, mainly French, to be the work of Gerson, although no conclusive evidence has been found to substantiate this belief.