The Battle of Pavia, was a battle between a Spanish-Imperial army under the nominal command of Charles de Lannoy plus the garrison of Pavia, commanded by Antonio de Leyv and the French army under the personal command of Francis I of France on the morning of 24 February 1525, it was the decisive engagement of the Italian War of 1521–26. In the four-hour battle, the French army was split and defeated in detail.

In January 1525, Lannoy was reinforced by the arrival of Georg Frundsberg with 15,000 fresh landsknechts and renewed the offensive. D'Avalos captured the French outpost at Sant'Angelo Lomellina, cutting the lines of communication between Pavia and Milan, while a separate column of landsknechts advanced on Belgiojoso and, despite being briefly pushed back by a raid led by Medici and Bonnivet, occupied the town. By 2 February, Lannoy was only a few miles from Pavia. Francis had encamped the majority of his forces in the great walled park of Mirabello outside the city walls, placing them between Leyva's garrison and the approaching relief army. Skirmishing and sallies by the garrison continued through the month of February. Medici was seriously wounded and withdrew to Piacenza to recuperate, forcing Francis to recall much of the Milan garrison to offset the departure of the Black Band; but the fighting had little overall effect. On 21 February, the Imperial commanders, running low on supplies and mistakenly believing that the French forces were more numerous than their own, decided to launch an attack on Mirabello Castle in order to save face and demoralize the French sufficiently to ensure a safe withdrawal.

Francis's precipitate advance, however, had not only masked the fire of the French artillery, but also pulled him away from the mass of French infantry, commanded by Richard de la Pole, and by Francois de Lorraine, who led the Black Band of renegade Landsknecht pikemen (not to be confused with the Italian mercenary company of arquebusiers by the same name), which was 4,000 to 5,000 men strong. D'Avalos, left in command of the Spanish forces after Lannoy had followed the retreating cavalry, formed his men up at the edge of the woods and sent messengers to Bourbon, Frundsberg, and De Vasto requesting assistance.

Frundsberg had meanwhile mauled the heavily outnumbered Swiss infantry opposing him; Tiercelin and Flourance were unable to hold their troops together, and the French foot began to flee the field.

By 8:00, a mass of Imperial pikemen and arquebusiers descended on the French cavalry from all sides. Lacking room to maneuver by the surrounding woods, the French gendarmes were surrounded and systematically killed. Richard de la Pole and Lorraine, advancing to assist Francis, were met by Frundsberg's arriving landsknechts; the French infantry was broken and routed, and de la Pole and Lorraine were both killed. In a particularly bitter contest between Imperial and renegade Landsknechts, the Black Band was surrounded by Frundsberg's pikemen and exterminated where it stood. The French king fought on as his horse was killed from under him by Cesare Hercolani, an Italian Condottiere. surrounded by Spanish arquebusiers, he was taken prisoner and escorted from the field.

The French defeat was decisive. Aside from Francis, a number of leading French nobles—including Montmorency and Flourance—had been captured; an even greater number—among them Bonnivet, Le Tremoille, La Palice, Richard de la Pole, and Lorraine—had been killed in the fighting. Francis was taken to the fortress of Pizzighettone.