Calvinism originated with the Reformation in Switzerland when Huldrych Zwingli began preaching what would become the first form of the Reformed doctrine in Zürich in 1519.

Zwingli and John Oecolampadius became embroiled in conflict over the real presence of Christ in the Eucharist with Martin Luther, leading to a division between Lutheran and Reformed Protestants. Several theologians succeeded Zwingli, the best known of which is John Calvin in Geneva, but other reformers like John Oecolampadius, Heinrich Bullinger, Peter Martyr Vermigli, and Wolfgang Musculus were also influential in the development of Reformed theology.

Reformed faith spread throughout Europe in the 16th century, with different character in different places. Calvinism was the dominant form of Protestantism in France. After a period of struggle, Calvinists were officially tolerated there. Under the leadership of John Knox, the Church of Scotland, which is Reformed, became the established church in Scotland. In the Netherlands, Calvinism also became the official established religion following a period of persecution. During the Reformation, Calvinism was the primary Protestant faith in Belgium but was eradicated in favor of the Counter-Reformation. Germany remained predominantly Lutheran during the 16th century, but Reformed worship was promoted intermittently by rulers in Electoral Palatinate, Margraviate of Brandenburg, and other German states. Reformed ideas also influenced Protestants in Eastern Europe, especially Hungary and Romania. The reform of the Church of England was also influenced by Reformed theologians, and remained so throughout the 16th century.