Catherine de' Medici entered the French court through her marriage to the future Henry II in 1533. During his reign from 1547 she was queen consort, but his mistress Diane de Poitiers exercised considerable influence. Henry's death in a tournament accident in 1559 transformed Catherine's position. Their son Francis II succeeded him, and after Francis's death in 1560 she became regent for the young Charles IX. Her principal aim was to preserve the Valois dynasty amid competition among powerful noble families and religious factions.

Catherine initially sought accommodation between Catholics and Huguenots. She supported the colloquy at Poissy in 1561 and an edict allowing limited Protestant worship in 1562. Neither measure overcame distrust, and the killing of Protestants at Vassy helped precipitate the French Wars of Religion. Through successive conflicts she negotiated settlements and marriages, balanced rival leaders, and attempted to maintain the crown's independence.

The marriage of her daughter Marguerite to the Protestant Henry of Navarre in August 1572 was intended to help secure peace. Instead, an attack on Admiral Gaspard de Coligny and fears of renewed conflict led the royal council to authorize the killing of Protestant leaders. The St. Bartholomew's Day massacre then spread far beyond the initial targets in Paris and into provincial cities. Catherine was involved in the decision at court, but the degree of her planning and control remains disputed. Responsibility for an advance plan to massacre all Huguenots should not be asserted as settled fact.

After Charles IX's death in 1574, Catherine continued to advise Henry III and traveled to negotiate with political opponents. Her influence diminished as the Catholic League and Henry's own policies transformed the conflict. She supported elaborate festivals and substantial artistic and architectural commissions, including the Tuileries Palace and work at Chenonceau.

Catherine died at Blois in January 1589 shortly after Henry III ordered the killing of the Duke of Guise and his brother. Her career was therefore defined less by independent territorial expansion than by governing, negotiating, and projecting royal authority through a prolonged civil crisis. Later portrayals often reduced her to a sinister foreign intriguer; a balanced account must consider the pressures on the crown while retaining her responsibility for coercion and the violence of the monarchy's religious policy.