Renaissance popes and advisers were not blind to the need for church reforms, but they resisted calls for a general council representing the entire church, fearing loss of power, revenue, and prestige. This changed beginning with Pope Paul III (pontificate 1534–1549), under whom the papal court became the center of the reform movement rather than its chief opponent.

In 1542 Pope Paul III established the Supreme Sacred Congregation of the Roman and Universal Inquisition, often called the Holy Office, with jurisdiction over the Roman Inquisition, a powerful instrument of the Catholic Reformation. The Inquisition was a committee of six cardinals with judicial authority over all Catholics and the power to arrest, imprison, and execute. Within the Papal States, the Inquisition effectively destroyed heresy (and some heretics).

Pope Paul III also called a general council, which met intermittently from 1545 to 1563 at Trent, an imperial city close to Italy. It was called not only to reform the church but also to secure reconciliation with the Protestants. Lutherans and Calvinists were invited to participate, but their insistence that the Scriptures be the sole basis for discussion made reconciliation impossible.

Nonetheless, the decrees of the Council of Trent laid a solid basis for the spiritual renewal of the Catholic Church. It gave equal validity to the Scriptures and to tradition as sources of religious truth and authority. It reaffirmed the seven sacraments and the traditional Catholic teaching on transubstantiation (the transformation of bread and wine into the body and blood of Christ in the Eucharist). It tackled the disciplinary matters that had disillusioned the faithful, requiring bishops to reside in their own dioceses, suppressing pluralism and the selling of church offices, and forbidding the sale of indulgences. Clerics who kept concubines were to give them up, and bishops were given greater authority. The council also required every diocese to establish a seminary for educating and training clergy. Seminary professors were to determine whether candidates for ordination had vocations, genuine callings to the priesthood. This was a novel idea, since from the time of the early church, parents had determined their sons’ (and daughters’) religious careers. Finally, great emphasis was placed on preaching to and instructing the laity, especially the uneducated. One decision had especially important social consequences for laypeople. The Council of Trent stipulated that for a marriage to be valid, consent (the essence of marriage) as given in the vows had to be made publicly before witnesses, one of whom had to be the parish priest. Trent thereby ended the widespread practice of secret marriages in Catholic countries. For four centuries the doctrinal and disciplinary legislation of Trent served as the basis for Roman Catholic faith, organization, and practice.