He was primarily educated in Luxembourg before attending Ampleforth College in the United Kingdom.
During WWII, the heir apparent to the Luxembourg throne evacuated to France before traveling to Canada to study political science at Université Laval. Two years after fleeing to Canada, the future Grand Duke went to England, where he joined the British Army as a volunteer in the Irish Guards, where he was commisioned as a Lieutenant in March 1943, and was promoted as a captain in 1943. The future Grand Duke took part in the Battle for Caen and the liberation of Brussels, as well as the liberation of Luxembourg. After the war was over until his abdication in 2000, he served as a Colonel of the Regiment of the Irish Guards (a position now held by Prince William, The Duke of Cambridge), and was often seen riding in uniform behind Queen Elizabeth during the Sovereign's Birthday Parade.
Upon his mother, Grand Duchess Charlotte's, abdication on 12 November 1964, he became Grand Duke of Luxembourg. His reign lasted from November 1964 to October 2000, upon his own abidication in favor of his son, now Grand Duke Henri.
He married Princess Joséphine-Charlotte of Belgium (1927–2005) in April 1953. Together, they had three sons and two daughters:
- Princess Marie-Astrid (1954), who married HI&RH Carl Christian Marcus d'Aviano, Prince Imperial and Archduke of Austria (born 1954) and has five children, and several grandchildren:
- Archduchess Marie Christine Anne Astrid Zita Charlotte of Austria , Countess of Limburg-Stirum (1983), married with two sons:
- Count Léopold de Limburg-Stirum ( 2011)
- Count Constantin de Limburg-Stirum (2013)
- Archduke Imre Emanuel Simeon Jean Carl Marcus d'Aviano of Austria (1985), married Kathleen Walker in 2012, and they have a daughter:
- Archduchess Maria-Stella of Austria (2013)
- Archduke Christoph Henri Alexander Maria Marcus d'Aviano of Austria (1988), married Adélaïde Drapé-Frisch in 2012
- Archduke Alexander Hector Marie Karl Leopold Marcus d'Aviano of Austria (1990)
- Archduchess Gabriella Maria Pilar Yolande Joséphine Charlotte of Austria (1994).
- Grand Duke Henri (1955), who married Grand Duchess Maria Terea, and has five children and three grandchildren:
- Prince Guillaume, Hereditary Grand Duke (1981), married Princess Stéphanie, Hereditary Grand Duchess in 2012
- Prince Félix (1984), married to Princess Claire in 2013. They have one daughter:
- Princess Amalia of Nassau (2014)
- Prince Louis(1986), who married Tessy Antony in 2006, with whom he has two sons:
- Prince Noah de Nassau (2006)
- Prince Gabriel de Nassau (2009)
- Princess Alexandra (1991)
- Prince Sébastien (1992)
- Prince Jean (1957) (renounced his and his descendants rights for the throne in 1986)
- Princess Marie-Gabrielle of Nassau (1986)
- Prince Constantin Jean Philippe Marie Albert Marc d'Aviano of Nassau (1988)
- Prince Wenceslas François Baudoin Léopold Juraj Marie Marc d'Aviano of Nassau (1990)
- Prince Carl-Johan Félix Julien Marc d'Aviano of Nassau (1992)
- Princess Margaretha (1957), married Prince Nikolaus of Liechtenstein, with the following children:
- Prince Leopold Emmanuel Jean Marie of Liechtenstein (1984-1984).
- Princess Maria-Anunciata Astrid Joséphine Veronica of Liechtenstein (1985).
- Princess Marie-Astrid Nora Margarita Veronica of Liechtenstein (1987)
- Prince Josef-Emanuel Leopold Marie of Liechtenstein (1989)
- Prince Guillaume (1963), married Sibilla Weiller, have the following children:
- Prince Paul Louis Jean Marie Guillaume of Nassau (1998)
- Prince Léopold Guillaume Marie Joseph of Nassau (2000)
- Princess Charlotte Wilhelmine Maria da Gloria of Nassau (2000)
- Prince Jean André Guillaume Marie Gabriel Marc d'Aviano of Nassau (2004)