Élisabeth Charlotte was finally married on 13 October 1698 at the Palace of Fontainebleau to Leopold, Duke of Lorraine.
The marriage was the result of the Treaty of Ryswick, one of its conditions being that the Duchy of Lorraine, which had been for many years in the possession of France, be restored to Leopold Joseph, a son of Charles V, Duke of Lorraine. Thus, Élisabeth Charlotte was but an instrument to cement the peace treaty. Her mother later said that her daughter "was a victim of war".
The marriage was seen as a brilliant match by the House of Lorraine but was regarded by some as a rank not deserved for a petite-fille de France.
To everyone surprise, what had been expected to be an unhappy union turned out to be a marriage of love and happiness. With the birth of her children, Élisabeth Charlotte showed great maternal instinct and a naturally caring character.
The marriage produced thirteen children, of which five survived into adulthood. Three of them died within a week in May 1711 due to a smallpox outbreak at the Château de Lunéville, the country seat of the Duke's of Lorraine.
After ten years, however, her husband turned his attentions to another, Anne-Marguerite de Lignéville, princesse de Beauvau-Craon. Embarrassed, Élisabeth Charlotte, on her mother's advice, remained silent and continued to live in the Château de Lunéville with her husband and his mistress. After her husband's liaison ended, the couple had five more children, one of whom would become the father of Queen Marie Antoinette.
Her husband died in 1729, leaving his wife Regent of Lorraine for their son, Francis Stephen of Lorraine.
Élisabeth Charlotte tried to engage her youngest child Anne Charlotte to King Louis XV; this project failed due to the intrigues of Duke of Bourbon; Élisabeth Charlotte then tried to arrange the marriage of Anne Charlotte to her first cousin Louis d'Orléans, Duke of Orléans, who had been recently widowed; Louis d'Orléans refused.