The siege of Pavia (27 October-24 February 1525) saw the defenders of the city hold long enough for Imperial reinforcements to read Italy before inflicting a crushing defeat on Francis I at the Battle of Pavia (24 February 1525).
In the aftermath of the failure of the Imperial siege of Marseille (July-August/ September 1524) Francis I invaded north-western Italy via the Argentière Pass, at the head of around 40,000 men. The main Imperial army, commanded by the Constable of Bourbon and Ferdinando Francesco d'Avalos, Marquis of Pescara withdrew to the River Adda while a strong garrison was left in Pavia, commanded by Antonio de Leyva. Francis had two main choices - attack the main Imperial army before it could be reinforced or besiege Pavia. He chose to attack Pavia, on the hope that the German garrison wouldn't hold out for long. This would have put pressure on Pope Clement VII, then an Imperial supporter, and also potentially open the road to Naples.
Francis began the siege with around 40,000 men. The siege began on 28 October, and the first artillery bombardment began on 6 November. Soon after this Francis made a crucial mistake, detaching about 15,000 men under John Stuart, Duke of Albany, south to invade Naples as part of a new alliance he had agreed with the Pope. This left Francis with 25,000 men. Albany's men would make no progress in Naples, but they would be badly missed when Imperial reinforcements arrived at Pavia early in 1525.
At first Francis conducted an active siege. He launched one assault on the city, which was repulsed. He then attempted to divert the River Ticino, which protected the southern side of Pavia, but this also failed. The artillery bombardment made extensive use of the new technique of the 'sap trench' (angled trenches designed to get close to the walls without exposing the attackers to fire from the walls), but eventually he settled down to conduct a blockage in the hope of starving the garrison out over the winter of 1524-25.
Instead the defenders gave time for Imperial reinforcements to reach Italy from Germany, under the command of Georg von Frundsberg, while Charles de Lannoy, viceroy of Naples, also arrived with Spanish and Italian troops (despite Albany's move south). At the same time French reinforcements were blocked, and an attack on Chiavenna forced France's Grison allies to pull back.
On 24 January 1525 the reinforced Imperial army left Lodi. The army advanced towards Milan then turned towards Pavia, camping east of the city. Francis was now unable to maintain a strict blockade of Pavia, and the Imperialists were able to get supplies into the city.
Even so the situation in Pavia was still desperate and the Imperial commanders decided to attack. On the night of 23-24 February then outflanked the French by breaking through the walls of the part of Mirabello. The resulting battle of Pavia (24 February 1525) ended as a crushing Imperial victory. Francis himself was captured, and eventually taken to Spain, where he was forced to sign the Treaty of Madrid (1526). Francis continued to fight in Italy for the rest of his reign, but was never really able to regain the ground he lost at Pavia in 1525.