Throughout the sixteenth century war between Catholics and Protestants would rend the kingdom.
In the 14th century, Vendôme united with the Bourbon through a double marriage. Jean VII of this new Bourbon-Vendôme family undertook the restoration of the chateau and its defenses. He redid the interior of the keep and added an elegant stairway, which connected the different levels of the chateau.
The wars of religion between Catholics and Protestants raged all the length of the sixteenth century and devastated the kingdom.
Despite the conversion to Protestantism of Jeanne d'Albret, the mother of Henri of Navarre and duchess of Vendome, the territory remained ferociously Catholic. When in 1598, the young King of Navarre, and Duke of Vendome, after swearing faith, became King of France under the name of Henry IV, his subjects refused to recognize him as King. Furious to be defied, he marched on the Loir Valley at the head of his army. There, one by one, he sieged and dismantled the fortresses of Vendome, Lavardin and Montoire.