Nicholas François de Lorraine-Vaudemont was the youngest son of duke Francis II of Lorraine, and as it appeared unlikely that he would succeed to the duchy, he was destined to the church. He was made coadjutor bishop of Toul, in spite of his youth, in 1619 and succeeded to the see in 1624, but never actually received any sacred orders. He studied at the University of Pont-à-Mousson, 1622—1629 towards doctorates in philosophy and theology. He returned to Nancy in June 1629. The thesis he prepared on the sacrament of penance was printed in Holland in 1627 with a dedication to Pope Urban VIII. After his promotion to the cardinalate, received private lessons from two Jesuit priests.
He was created cardinal January 19, 1626, but reserved in pectore and not published until August 30, 1627. He never received the red hat and the cardinal-deaconry. When in 1634 his brother Charles was pressured into resigning his estates in his favor, and he became duke of Lorraine, he wrote to Urban VIII, March 4, 1634, resigning the cardinalate for having married his cousin Claude Françoise de Lorraine, the second daughter of Henri, duke of Lorraine and Bar, on February 17-18. On March 8, 1634, the pope declared him in nullo e sacris ordinis constitutum, depriving him of the cardinalate and the administration of the diocese of Toul. In the consistory of March 22, 1634, the pope communicated the news to the cardinals.
In 1661 he himself abdicated the throne, making way again for his older brother, Charles IV, Duke of Lorraine.