Frederick Augustus died in 1816 and Wilhelm inherited the Usingen territories and became sole sovereign of the Duchy of Nassau.

He is the father of Adolphe, Grand Duke of Luxembourg, and Queen Sophia of Sweden and Norway, consort of King Oscar II and a 3rd cousin of William III of the Netherlands, who left a surviving daughter to rule his main realm, but the crown of Luxembourg went through the male line, looking to 17 generations back, to pass to the Duke of Nassau and then his descendants.

Wilhelm was the eldest son of Frederick William, Duke of Nassau, and Burgravine Louise Isabelle of Kirchberg.

With the Nassau troops, he was involved on the Seventh Coalition's side in the Battle of Waterloo against Napoleon.

When his cousin and co-Duke died on 24 March 1816, Wilhelm inherited the Usingen territories and became sole ruler of the Duchy of Nassau.