In 1736 her brother the Duke of Lorraine married the Archduchess Maria Theresa of Austria, daughter and heiress apparent of Charles VI, Holy Roman Emperor. The union between the House of Lorraine and the House of Habsburg was used to ensure a more prestigious marriage for the unwed princess. The already twice widowed Charles Emmanuel III of Sardinia asked for her hand in late 1736 and the marriage went ahead.
She married the king of Sardinia by proxy on 5 March 1737 at Lunéville with the Prince of Carignan acting as the king, who was the prince's brother-in-law. The day after the proxy marriage, she left for Lyon where she arrived on 14 March. Her brother the Duke of Lorraine raised a dowry for her and the marriage contract was signed in Vienna by the Duke and Duchess of Lorraine and Emperor Charles VI.
The couple married in person on 1 April 1737. Charles Emmanuel III was her first cousin, his mother being Anne Marie d'Orléans – a half sister of her mother Élisabeth Charlotte. The marriage produced three children, only one of whom survived infancy but had no further progeny. She and her husband arrived in Turin on 21 April.
Elisabeth Therese died at the Palace of Venaria aged 29, having fallen ill with puerperal fever after childbirth. She was buried in the Cathedral of Saint Giovanni Battista in Turin. She was moved to the Royal Basilica of Superga in 1786 by her stepson Victor Amadeus III.