In the 1520s during the Protestant Reformation, the city, under the political guidance of Jacob Sturm von Sturmeck and the spiritual guidance of Martin Bucer embraced the religious teachings of Martin Luther. Their adherents established a Gymnasium, headed by Johannes Sturm, made into a University in the following century. The city first followed the Tetrapolitan Confession, and then the Augsburg Confession. Protestant iconoclasm caused much destruction to churches and cloisters. Strasbourg was a centre of humanist scholarship and early book-printing in the Holy Roman Empire, and its intellectual and political influence contributed much to the establishment of Protestantism as an accepted denomination in the southwest of Germany. (John Calvin had spent several years as a political refugee in the city). Together with four other free cities, Strasbourg presented the confessio tetrapolitana as its Protestant book of faith at the Imperial Diet of Augsburg in 1530, where the slightly different Augsburg Confession was also handed over to Charles V, Holy Roman Emperor.
After the reform of the Imperial constitution in the early sixteenth century and the establishment of Imperial Circles, Strasbourg was part of the Upper Rhenish Circle, a corporation of Imperial estates in the southwest of Holy Roman Empire, mainly responsible for maintaining troops, supervising coining, and ensuring public security.
After the invention of the printing press by Johannes Gutenberg around 1440, the first printing offices outside the inventor's hometown Mainz were established around 1460 in the Alsatian capital by pioneers Johannes Mentelin and Heinrich Eggestein. Subsequently, the first modern newspaper was published in Strasbourg in 1605, when Johann Carolus received the permission by the City of Strasbourg to print and distribute a weekly journal written in German by reporters from several central European cities
