Martin Luther (1483-1546) was ordained as a priest in 1507 and became a professor of biblical interpretation at the University of Wittenberg in 1508. Under Luther’s influence, the Wittenberg faculty of theology was committed to a program of theological reform based on "the Bible and St. Augustine." Luther also contributed to major theological reform by translating the Bible into vernacular German, which enabled the masses to hear and read the gospel of Jesus Christ in their own language.

In 1517, Luther launched a movement against the Catholic Church when he posted his 95 Theses, or Disputation on the Power and Efficacy of Indulgences, on the door of the castle church at Wittenberg.

In 1520, Pope Leo X warned Luther with the papal bull, an official papal document written in response to Luther's 95 Theses, ordering him to recant 41 sentences from his Theses and subsequent writings or face excommunication. Luther responded by publicly burning the document and was excommunicated in 1521.

The Lutheran confession of faith, the Augsburg Confession (1530), was mainly the work of Philipp Melanchthon, who, after receiving the approval of Martin Luther, presented it at Augsburg to the Emperor Charles V. To make the Lutheran position as inoffensive as possible to the Catholics, the Confession’s language was studiously moderate. A considerably revised text issued by Melanchthon in 1540 was accepted by the Reformed (Calvinist) churches in Germany.