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William II is also called "William the Middle" to distinguish him from his elder brother "William I the Elder", and his cousin "William III, the Younger". His parents were Louis II the Frank (1438–1471) and Mechthild, daughter of Count Louis II of Württemberg.
William II became Landgrave of Lower Hesse in 1493, after his brother William I resigned.
On 9 November 1497 William II married Yolande, daughter of Frederick II of Vaudémont. She died on 21 May 1500 after the marriage produced one child, William (27 March 1500 – 8 April 1500). The same year on 20 October, his second marriage was to Anna of Mecklenburg-Schwerin (14 September 1485 – 12 May 1525), who bore him three children: