Answer:
The Reformation
There were protests against the abuses of the Roman Catholic Church in the centuries before the 16th century, by men such as John Wycliffe in England (1330-1384) and Jan Hus in Bohemia (1369-1415). But the full-blown protest of "Protestants" caused the greatest stir in the 16th century, beginning with Martin Luther in the German territories and then Ulrich Zwingli and John Calvin in Switzerland.
Incidentally, the name "Protestant" came into usage after the Diet (days of meetings) at Speyer in 1529, when a policy change was made in the Holy Roman Empire, contradicting earlier decisions that had allowed greater freedoms to Lutheran princes in their territories. Those princes filed an official protest against the decisions made at Speyer, and thus the name "Protestants" began to be applied to their side.