More than 300,000 imperial troops moved east through Prussia as part of Napoleon's massive 600,000-man army for the invasion of Russia. The orderly requisition of Prussian goods and provisions soon collapsed under the strain, prompting the French to loot indiscriminately. Words fail to describe the devastation of the Prussian provinces, especially East Prussia. Atrocities that accompanied the rape of the land by Prussia's “ally” rivaled the human disaster of the Thirty Years War. The Hanoverian minister Ludwig von Ompteda noted that the French had left the Prussian peasants with “nothing but eyes to weep with in their misery.” The French also carried off the 20,842 soldiers who formed the Prussian contingent of the Grande Armée of 1812. Commanded by General Julius August von Grawert, the Prussian corps consisted of the best units drawn from the six brigades of the Prussian army, with the East Prussian regiments providing the largest contribution because their depots stood closest to the staging areas of the imperial army. Napoleon forced Frederick William to demobilize the rest of the Prussian army in accordance with the 42,000-man limit of the 1808 treaty. Thus, approximately 22,000 troops remained in Prussia, backed by a trained reserve of 36,424.

On the evening of 22 June 1812, the Grande Armée commenced the invasion of Russia. Poor health forced Grawert to turn over command to General Yorck. As the 27th Infantry Division of the Grande Armée, the Prussians served in Marshal Jacques-Étienne Macdonald's X Corps. While X Corps marched toward Riga, Napoleon led the main body of the Grande Armée in pursuit of the Russians, who implemented the defensive plans drafted by Phull and Barclay de Tolly. Although failing to destroy the Russian army at Borodino on 7 September, Napoleon reached an evacuated Moscow one week later. Not only did the tsar refuse to negotiate, but the Russians also had burned the city. Having to choose between remaining at Moscow – 1,200 miles from Paris – for the winter or withdrawing, the emperor chose the latter. On 19 October, a much smaller Grande Armée commenced the retreat.