He succeeded his brother John George II as duke of Saxe-Eisenach when he died childless in 1698.

[1] Saxe-Eisenach experienced a cultural boon under his reign, which was in no small part due to the duke's court band, whose most prominent member was Georg Philipp Telemann.

They had two children: In Wolfenbüttel on 27 February 1697 — two years of the death of his first wife — John William married secondly with Christine Juliane of Baden-Durlach, a daughter of Charles Gustav of Baden-Durlach.

They had seven children: In Weissenfels on 28 July 1708 — one year after the death of his second wife — John William married thirdly with Magdalene Sibylle of Saxe-Weissenfels, a daughter of Johann Adolf I, Duke of Saxe-Weissenfels.

They had three children: In the Schloss Philippsruhe on 29 May 1727 — one year after the death of his third wife — John William married fourthly with Marie Christine Felizitas of Leiningen-Dagsburg-Falkenburg-Heidesheim, Dowager Princess of Baden-Durlach.