The Gregorian reform that strengthened the independence of the Catholic Church in relation to the secular powers was intimately connected to the Investiture Controversy in late eleventh to early twelfth century Europe. This controversy started in 1073 with a conflict between Gregory VII and the German emperor, Henry IV; it ended with the Worms Concordat in 1122, which represented the political compromise between the papacy and the empire. The Investiture Controversy's most dramatic moment came in 1077 when the pope publicly humiliated Henry IV by making him stand in the snow at the gates of the Castle of Canossa for days as an act of repentance for his sins.

The papacy’s strength during the Investiture Controversy paved the way for its rise in political importance in the twelfth and the thirteenth centuries. The Catholic Church came to dominate Europe politically while remaining relatively independent from local and national feudal frameworks; this enhanced its ability to mobilize support for the other opponents of feudal politics, such as the rising communal movement in Italy (especially the Lombard League). The Lombard League of the North Italian urban republics and the papacy eventually became political allies; the pope supported the Lombard League in its war against the emperors of the Holy Roman Empire, such as Frederick I Barbarossa in the twelfth century and Frederick II Hohenstaufen in the thirteenth century.

While in France and England, the papacy supported the gradual concentration of political power in the hands of centralized national monarchies. In Italy and Germany the papacy supported decentralization. The prominent role that the papacy played in the high medieval politics of these countries contributed to the ongoing fragmentation of the German and Italian political landscape during the later Middle Ages and for a long time afterwards.

The major significance of this controversy was that it increased the degree of conflict between church and state.

This controversy was over who would get to appoint bishops and other church officials.  Church officials were very important and influential people and secular rulers naturally wanted to control them as much as possible.  For this reason, secular rulers wanted to be able to appoint them.  King Henry IV of Germany tried to appoint the bishop of Milan in 1075.  This infuriated Pope Gregory VII.  The Pope wanted to hold on to the power to appoint bishops so as to keep power for the church and away from the secular leaders.  In the course of this controversy, Gregory excommunicated Henry.  Henry, knowing this could weaken his hold on power, begged forgiveness and a compromise was reached.

This controversy led to more such struggles between the Church and the state as both sides attempted to gain more power.