Claude was born on 13 October 1499, eldest daughter of Louis XII of France and Anne of Brittany.
Because her mother had no surviving sons, Claude became heiress to the Duchy of Brittany. The crown of France, however, could pass only to and through male heirs, according to Salic Law. Eager to keep Brittany separated from the French crown, Queen Anne, with help of Cardinal Georges d'Amboise, promoted a solution for this problem. The Cardinal began a dispute with the Pierre de Rohan-Gié, the Marshal of Gié, who supported the idea of a marriage between the princess and the Duke of Valois, the heir of the French throne after Louis XII, and thus kept Brittany united to France.
On 10 August 1501 at Lyon was signed the marriage contract between Claude and the future Holy Roman Emperor Charles V by François de Busleyden, Archbishop of Besançon, William de Croÿ, Nicolas de Rutter and Pierre Lesseman, all ambassadors of Duke Philip of Burgundy, Charles' father. A part of the contract promised the inheritance of Brittany to the young prince, already the next in line to thrones of Castile and Aragon, Austria and the Burgundian Estates. In addition, the first Treaty of Blois, signed in 1504, gave Claude a considerable dowry in the -likely- case of Louis XII's death without male heirs: besides Brittany, Claude also received the Duchies of Milan and Burgundy, the Counties of Blois and Asti and the territory of the Republic of Genoa, then occupied by France. Thus, all the causes of the future rivalry between Charles V and Francis I have been decided even before the succession of the two princes.
In 1505, Louis XII, very sick, fearing for his life and not wishing to threaten the reign of his only heir, cancelled the engagement in the Estates Generals of Tours, in favour of the young Duke of Valois, the future Francis I. Indeed, previously Louise of Savoy obtained from the king a secret promise that Claude could be married to her son. Anne of Brittany, furious to see the triumph of Marshal of Gié, exerted all her influence to obtain his conviction for treason before the Parliament of Paris.
On 9 January 1514, when her mother died, Claude became Duchess of Brittany; and four months later, on 18 May, she married her cousin Francis at Saint-Germain-en-Laye. With this union, it was secured that Brittany would remain united to the French crown, if the third marriage of Louis XII with Mary of England, celebrated on 9 October 1514, would not produce the long-waited heir. However, the union was short-lived and childless: Louis XII died less than three months later, on 1 January 1515, reputedly worn out by his exertions in the bedchamber. Francis and Claude became king and queen.
Claude surrounded by her daughters,Charlotte, Madeleine and Marguerite, her sister Renée ,or her deceased older daughter Louise, and her husband's second wife Eleanor of Austria, in the Livre d'heures de Catherine de Medicis, 1550.
Queen Claude was eclipsed at court by her mother-in-law, Louise of Savoy, and her sister-in-law, the literary Margaret of Angoulême. She never ruled over Brittany; in 1515 she gave the government of her domains to her husband in perpetuity. Unlike her younger sister Renée, she seems to have never showed any interest in her maternal inheritance nor had any disposition to politics, as she preferred to devote herself to religion under the influence, according to some sources, of Christopher Numar of Forli, who was the confessor of her mother-in-law.
After Francis became king in 1515, Anne Boleyn stayed as a member of Claude's household.
Claude was crowned Queen of France at St. Denis Basilica on 10 May 1517 by Cardinal Philippe de Luxembourg, also known as Cardinal du Mans, who "anointed her in the breast and forehead".
She spent almost all her marriage in an endless round of annual pregnancies. Francis had many mistresses, but was usually relatively discreet.
Claude died on 20 July 1524 at the Château de Blois, aged twenty-four. Some alleged that she died in childbirth or after a miscarriage, others believed that she died for exhaustion after her many pregnancies or after suffering from bone tuberculosis, like her mother, or died from syphilis caught from her husband. She was buried at St. Denis Basilica.