In 1531 some princes (most notably Philip I of Hesse and John Frederick, Elector of Saxony) were opposed to the Emperor's attempt to restore religious and political unity in the German lands through the re-proposal of the Worms Edict.

This led to the formation of the Schmalkaldic League[8] (named after the town of Schmalkalden in Thuringia where the pact was stipulated), a militarily defensive alliance with a markedly anti-Habsburg and anti-Catholic stance.

The League meanwhile received support from several free cities (Bremen, Hamburg, Lübeck, Ulm and Strasbourg), wishing to affirm their independence from the central power.

In need of the military support of the German states in his war against the Ottoman Turks in the eastern regions of his lands, the Emperor chose not to oppose the League and to grant wide autonomy to it.

Martin Luther's death in 1546 and the temporary cessation of the Turkish threat from the east also put Charles in the best possible condition to focus on the internal enemy that endangered the religious and territorial unity of Imperial Germany.

With the beginning of spring Charles then marched toward Saxony to help Maurice's army and to end his clash with John Frederick, the last Protestant prince still opposing him.

However, hoping to encourage a Protestant and anti-imperial uprising in Bohemia, John Frederick took the decision to split his forces and he deployed a large portion of his troops there.

With the intention of reaching the well-defended stronghold of Wittenberg, the Elector then marched northwards, abandoning his position in Meissen and camping at the end of April at the town of Mühlberg, leaving only a few troops as guards on the bank of the Elbe river, that he considered too wide to be easily crossed by the imperial forces.

In addition to this, some veteran soldiers were able to prevent the demolition of a pontoon bridge built by the Saxons,[11] that was immediately used by the Imperial cavalry to pass safely to the other shore.

John Frederick chose to deploy his troops along the edge of a forest, in order to prevent a possible encirclement by the imperial cavalry and to have a safer escape route in case of retreat.

The battle began in the evening; the Saxon army, mainly made up of peasants, succeeded in repelling the first assaults of the Hungarian cavalry, but the greater number and better preparedness of Charles' soldiers, among the best in the world at that time, decided the fate of the clash.

Once the fragile wings of the Saxon army were defeated, the infantry tercios, placed at the center, had a good game in breaking enemy resistance, forcing the Protestants to retreat through the adjacent forest.

Some sources report that Emperor Charles V commented on the victory with the sentence Vine, vi y venció Dios (in Spanish "I came, I saw, and God won"), a paraphrase of the famous exclamation pronounced by Julius Caesar.