On 23 December 1588, Henri I, Duke of Guise was assassinated by the Quarante Cinq serving King Henri III. The event was one of the most critical moments of the French Wars of Religion. The duke had achieved, since 1584, considerable power over the kingdom of France, through his alliance with the Ligue movement, which he had co-opted for the cause of resisting the king's chosen successor of Navarre, a Protestant. Despite some effort to resist Guise and the ligue, Henri III had been forced by his weak position to accede to their continued demands. After the Day of the Barricades in May 1588, the ligue expelled Henri from Paris, and Henri was forced to make Guise lieutenant general of the kingdom, call an Estates General and sign an Edict of Union in July which prohibited Navarre from succeeding to the throne and outlawed Protestantism in France. Increasingly unable to bear the humiliations Guise and the ligue forced upon him, he was further outraged by the Estates General. The body, largely ligueur dominated, rejected his attempt to chastise Guise for forming associations, diverted tax income to Guise's cousin Mayenne and rejected all compromise with the king.
These indignities in combination with the increasingly cavalier attitude of much of the Guise family, who spoke of deposing him and interring him in a monastery, persuaded Henri to have the duke killed. To accomplish this, he required a time when Guise was alone, something that could only be accomplished at a meeting of the council. Feigning an intention to leave Blois for Christmas, he persuaded Guise to come to a council meeting on 23 December. Guise received numerous warnings of the king's intentions for the meeting, but was unable to imagine that the pious and compliant Henri would dare touch him. Shortly after the meeting began, Guise was called away to meet the king. En route to the king he was attacked by several members of the king's bodyguard, the Quarante Cinq and murdered. His brother, the Cardinal de Guise and their ally the Archbishop of Lyon heard the fight in the next room, but were apprehended before they could aid their friend and brother. While the king prevaricated over what to do with Cardinal Guise he eventually decided that the Cardinals threats against him warranted his death, and he was murdered in his cell the following day. The two men's ashes were then scattered into the Loire.
While the estates were quickly cowed from reacting with any fury to this royal coup, with the prominent ligueurs in their midst arrested. The rest of France was not so easily quieted. The Seize which had controlled Paris since the Day of the Barricades declared that they would have their vengeance against the murderer of the princes. The organisation quickly moved to purge the Paris Parlement of royalist sympathisers, making the body ligueur. The Sorbonne for its part, pre-empted a Papal declaration of Henri's excommunication for the murder of the Cardinal by declaring that all subjects were released from their oath of obedience, and that it was their duty to fight Henri de Valois. Across the kingdom the majority of the fifty largest urban centres in the country defected to the ligue. In Paris the furious Catholic population destroyed any public monument, image or symbol that represented the king, while pamphleteers denounced him as a Herod, Nero and anti-Christ, with some going so far as to say that he should be killed. The Pope for his part was furious at the murder of the Cardinal, and despite the king sending several representatives to convince him, threatened excommunication in thirty days unless Henri came to Rome to explain himself. Henri for his part made an alliance with Navarre, and the two set forth to reconquer Paris. Putting the city to siege on 29 July, Henri was assassinated by a radical Catholic friar, energised by the hatred in the city, on 1 August 1589.