In 1560, Catherine de Medici became regent for her young son Charles IX. Catherine felt that she had to steer the throne carefully between the powerful and conflicting interests that surrounded it. Although she was a sincere Roman Catholic, she was prepared to deal favourably with the Huguenot House of Bourbon in order to have a counterweight against the overmighty House of Guise. She therefore was led to support religious toleration in the shape of the Edict of Toleration in 1562. In March, the Guise faction attacked an Huguenot service at Vassy and committed a general massacre. This provoked a response from the Bourbons, who, led by Condé, organised a kind of protectorate over the Protestant churches and began to garrison strategic towns along the Loire. Here, at Dreux and at Orleans, there were the first major engagements; at Dreux, Condé was captured by the Guises and Montmorency, the governent general, by the Bourbons. At Orleans, the Duke of Guise was killed, and Catherine's fears that the war might drag on led her to negotiate a truce and the Edict of Amboise (1563).
This was generally regarded as unsatisfactory by all concerned, the Catholics in particular being uneasy about what they regarded as unwise concessions to the heretics. The political temperature of the surrounding lands was rising, as unrest grew in the Netherlands. The Huguenots became suspicious of Spanish intentions when the latter reinforced their strategic corridor from Italy north along the Rhine, and made an unsuccessful attempt at taking control of the king. This provoked a further outburst of hostilities which ended in another unsatisfactory truce, the Peace of Longjumeau (March 1568).
In September of that year, war again broke out, and Catherine and Charles decided to throw in their lot with the Guises. Religious toleration was once more at an end, and the Huguenots fought the Catholics to another standstill signalled by the Peace of St Germain (August 1570).
Matters became complicted thereafter as Charles IX warmed to the Huguenot leaders, especially Gaspard de Coligny, as his mother became suspicious and eventually alarmed. When it became clear that the king was bent on a full-scale alliance with England and the Dutch rebels, Catherine plotted the assassination of Coligny. The attempt was made on August 22 1572. It failed, and Charles was persuaded that the Huguenots would take revenge against the crown. In fact, many Huguenots were in Paris for the marriage of Marguerite de Valois to Henry of Navarre. Told that it was a necessary pre-emptive strike, Charles approved of a massacre of the Protestants. This became known to history as the St. Bartholomew's Day Massacre. Throughout August 23 Huguenots were slaughtered in their thousands (probably around 3,000) in Paris, and, in the days that followed, many more in the provinces.
Both Philip II of Spain and Pope Gregory XIII declared themselves well pleased with the outcome, which was naturally viewed with horror by their religious opponents throughout Europe. In France, it solidified Huguenot opposition to the crown.
Charles IX died in May of 1574, and Henry III succeeded him. Henry soon found himself with the same problem of trying to maintain royal authority in the face of the competing factions. The Guises, who had formed the Catholic League, had the unwavering support of the Spanish superpower and were therefore in a very strong position throughout the 1580s. The Huguenots, however, had the advantage of a regional power base in the south west - they were supported in principle by outside Protestant forces, but in practice the other Protestant powers such as England or the German states could bring no useful forces to bear.
Things came to a head again in 1584, with the death of Henry's younger brother, who was the heir to the throne as Henry had no children. Disastrously, from the Catholic perspective, that left Henry of Navarre as heir. As the head of the Guise family was also a Henry, this period of the wars is called the "War of the Three Henries". The king at first tried to put himself at the head of the Catholic League, while remaining in favour of a moderated settlement. This was anathema to the Catholic extremists, who wanted the Huguenots completely suppressed. In May 1588, Paris rose against the king and in favour of the Guises; the king left the city. The Guises then proposed a settlement with a cipher as heir, and demanded a meeting of the States General, which took place at Blois in December of that year.
At Blois, Henry of Guise was lured into a trap and assassinated. The Catholic League went into a frenzy and the Sorbonne declared it a pious act to assassinate the king, a declaration reminiscent of the Papal bull Regnans in Excelsis against Elizabeth I. In July 1589, Henry was assassinated, but lived long enough to name Henry of Navarre as heir to the throne.
The situation on the ground in 1590 was that King Henry IV of France, as Navarre had become, held the south and west, and the Catholic League the north and east. The new king knew that he had to take Paris if he stood any chance of reuniting the kingdom. Paris was besieged, but the siege was lifted with Spanish support. Realising that there was no prospect of a Protestant king succeeding in fanatically Catholic Paris, Henry, with the famous phrase "Paris vaut bien une messe", announced his conversion to the old faith and was crowned at Chartres in 1594.
The League fought on, but enough moderate Catholics were won over by the conversion to make their party ultimately one of extremists only. The Spanish withdrew from France under the terms of the Peace of Vervins. Henry was faced with the task of reuniting France under a single authority. The essential first step in this was the negotiation of the Edict of Nantes, which, rather than being a kind of genuine toleration, was in fact a kind of permanent truce between the religions, with guarantees for both sides. The Edict can be said to mark the end of these civil wars.