The War of the League of Cognac (1526–30) was fought between the Habsburg dominions of Charles V—primarily the Holy Roman Empire and Spain—and the League of Cognac, an alliance including the Kingdom of France, Pope Clement VII, the Republic of Venice, the Kingdom of England, the Duchy of Milan, and the Republic of Florence.

The Sack of Rome, then part of the Papal States, followed the capture of the city on 6 May 1527 by the mutinous troops of Charles V, Holy Roman Emperor, during his war with the League of Cognac, known as the War of the League of Cognac. Despite being ordered not to storm the city, with Charles V intending to only use the threat of military action to make Pope Clement VII come to his terms, a largely unpaid Imperial army formed by 14,000 Germans, many of them Lutheran, 6,000 Spaniards and some Italian contingents occupied the scarcely defended Rome and began looting, slaying and holding citizens for ransom in excess without any restraint. Clement VII took refuge in Castel Sant'Angelo after the Swiss Guard were annihilated in a delaying rearguard action; he remained there until a ransom was paid to the pillagers.