The Protestant Reformation permanently divided western Christendom along religious lines and helped to foster modern Europe's collection of often mutually antagonistic nation-states. Many scholars have argued that the Reformation's significance was not only religious, but that it also had a major political, social and economic impact on western history. Protestantism generally rejected the Church's mediating role between God and humankind, instead placing the individual believer alone before the judgment and mercy of God. Therefore, Protestantism may well have appealed to those with little invested in the traditional structures of authority and society. But Protestantism was never a monolithic movement. The Protestant leaders quickly fell out among themselves over matters of religious belief and practice, and over the social and political implications of faith. After Martin Luther's death in 1545, the leadership of aggressive international Protestantism came increasingly from John Calvin's Geneva, while the Lutherans became more insular, and were mostly restricted to northern Germany and Scandanavia. The Peace of Augsburg in 1555, which granted official toleration to Lutherans in the Holy Roman Empire, accentuated this trend.

Even before the German monk nailed his Ninety-Five Theses to the door in Wittenberg, many Catholics (influenced by Renaissance humanism) had called for reform of the Roman Catholic Church. Following Martin Luther's enormously influential challenge to Catholicism in 1517, the cardinals, bishops and Pope at the head of the Church of Rome had finally to decide upon a course of action. Some Catholics saw a certain degree of truth in Luther's criticisms and believed this would be a good opportunity to reform and reinvigorate the Church from within. More conservative Catholics, however, felt that the best way to confront Protestantism was to strengthen the Church hierarchy and attempt to eliminate any heretics. The tension between reconciliation and repudiation can be seen in many of the official Church documents of the mid-sixteenth century. By the end of the Council of Trent in 1563, however, the conservatives seemed to have won the day and the Roman Catholic Church entered a period marked by staunch conservatism, centralized papal authority, and a desire to eradicate heresy in what was left of Catholic Europe.

In the aftermath of the beginning of the Protestant Reformation, the century between 1550 and 1650 was one of disorder and distrust. Since political authority rested on the support of religious authorities, all religious conflicts were also political struggles, and such conflicts divided people throughout Europe. In France, religious uprisings and civil war pitted nobles against nobles and involved the common people in bloody combat with their neighbors. In the Netherlands, war with the Spanish Habsburgs raged. England faced pressures from radical Protestants on one side and persecuted Catholics on the other. Finally, within the Holy Roman Empire the fierce battles of the Thirty Years' War tore up the German countryside, devastated the population, and ended in a religious stalemate. Moreover, this period witnessed a dramatic escalation in the persecution of women and a smaller number of men for alleged witchcraft. Between 1550 and 1650, 100,000 people were tried and about 60,000 were executed for this crime in Germany, Switzerland, Poland, France, and Scotland. Religious fears and class divisions marked this period of religious warfare and witch craze. Only with the Peace of Westphalia of 1648 and the decrease of witch hunts around 1650 would the history of the Reformation finally reach its conclusion.