By the time of the Protestant Reformation in the 16th century, Strasbourg was a prosperous community, and its inhabitants accepted Protestantism in 1523. Martin Bucer was a prominent Protestant reformer in the region. His efforts were countered by the Roman Catholic Habsburgs who tried to eradicate heresy in Upper Alsace. As a result, Alsace was transformed into a mosaic of Catholic and Protestant territories. On the other hand, Mömpelgard (Montbéliard) to the southwest of Alsace, belonging to the Counts of Württemberg since 1397, remained a Protestant enclave in France until 1793.

When did Strasbourg accept Protestantism?