He was born in Weimar, the eldest son of Johann Ernst II, Duke of Saxe-Weimar and Princess Christine Elisabeth of Schleswig-Holstein-Sonderburg.

When his father died in 1683, he succeeded him as duke; however, he was compelled to rule jointly with his younger brother Johann Ernst III.

Six months after the death of his father (2 November 1683), William Ernest married in Eisenach with Charlotte Marie, his cousin and eldest surviving daughter of his uncle Bernhard II, Duke of Saxe-Jena, in order to secure the family lands.

The composer Johann Sebastian Bach worked for the duke from 1708, first as organist, then as Konzertmeister (leader of the orchestra) in Weimar.

Two months later, on 4 November, duke John William of Saxe-Jena (Charlotte Marie's brother), died without heirs, and Wilhelm Ernst took possession of part of his duchy after a treaty was signed with the Saxe-Eisenach branch of his family.