He was originally destined for an ecclesiastical career, being made bishop of Metz in 1543 and of Verdun in 1544. In June 1545, he became joint "tutor and administrator" for his nephew, Charles III, Duke of Lorraine, with his sister-in-law Christina of Denmark. However, the Estates of Lorraine, in November 1545, removed him in favor of Christina as sole regent. He opposed her pro-Imperial policies. Resigning his dioceses in 1548 in favor of his uncle Jean, Cardinal of Lorraine, he took the title Count of Vaudémont.
After seizure of the Three Bishoprics in 1552 by Henry II of France, he was re-appointed as sole regent for his nephew, a position he retained until 1559.
In 1551, Nomeny was detached from the Bishopric of Metz and given to him as a margraviate by Maximilian II, Holy Roman Emperor in 1567, in right of which he was recognized as an independent, hereditary Prince of the Empire (the House of Lorraine would obtain a full vote in the Imperial Diet in 1736 for Nomeny in compensation for cession of the Duchy of Lorraine to France—in addition to acquisition of the Grand Duchy of Tuscany).
In France, his mother's barony of Mercœur was likewise elevated to the status of a princedom (though not independent of the French crown) in 1563, and raised to a ducal peerage in 1569. He was also created a knight of the Order of Saint Esprit.
He married thrice. His first marriage, on 1 May 1549 in Brussels, was to Marguerite d'Egmont (1517 – 10 March 1554, Bar-le-Duc), daughter of Count Jean IV of Egmont. By her he had one son and three daughters:
- Marguerite of Lorraine (b. 9 February 1550), d. young.
- Catherine of Lorraine (b. 26 February 1551, Nomeny), d. young.
- Henri of Lorraine (b. 9 April 1552, Nomeny) Count of Chaligny, d. young.
- Louise of Lorraine (30 April 1553, Nomeny – 29 January 1601, Château de Moulins), married on 13 February 1575, at Reims, Henry III of France.
His second marriage was on 24 February 1555 at Fontainebleau, to Joanna of Savoy (1532–1568), daughter of Philippe, Duke of Nemours. By this marriage he had four sons and two daughters:
- Philippe Emmanuel of Lorraine, Duke of Mercœur (1558–1602).
- Charles de Lorraine (20 April 1561, Nomeny – 29 October 1587, Paris), known as the Cardinal de Vaudémont, Bishop of Toul and of Verdun.
- Jean of Lorraine (b. 14 September 1563, Château de Deneuvre), d. young.
- Marguerite of Lorraine (14 May 1564, Nomeny – 20 September 1625), married on 24 September 1581 in Paris Anne, Duke of Joyeuse (1561–1587), married on 31 May 1599 François de Luxemburg, Duke of Piney (d. 1613).
- Claude of Lorraine (b. 12 April 1566, Nomeny), d. young.
- François of Lorraine (15 September 1567–1596, Châtel-sur-Moselle), Marquis of Chaussin.
His third marriage was on 11 May 1569 at Reims, to Catherine of Lorraine(1550–1606), daughter of Claude, Duke of Aumale. By her he had three sons and two daughters:
- Henri of Lorraine (31 July 1570, Nancy – 26 October 1600, Vienna), Marquis of Mouy and Count of Chaligny, married on 19 September 1585 Claude de Mouy.
- Christine of Lorraine (b. 24 September 1571, Château de Koeurs), d. young.
- Antoine of Lorraine (27 August 1572–1587, Mainz), Abbot of Beaulieu and Bishop of Toul.
- Louise of Lorraine (b. 27 March 1575, Nancy), d. young.
- Eric de Lorraine (14 March 1576 – 27 April 1623), Bishop of Verdun.
elevated from Barony
|Prince of Mercœur
elevated to Duke
|Count of Vaudémont
|Margrave of Nomeny
elevated from Princedom
|Duke of Mercœur
Read more about this topic: Nicolas, Duke Of Mercœur
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