In the 15th century, much of what is now the German state of Thuringia, including the area around Eisenach, was in the hands of the Wettin dynasty, since 1423 Prince-electors of Saxony.

However, when Ernest's grandson John Frederick the Magnanimous revolted against Emperor Charles V during the Schmalkaldic War, he was defeated at the 1547 Battle of Mühlberg and deprived of the electorate in favour of his Wettin cousin Maurice.

All descendants of John Frederick the Magnanimous in the male line bore the title "Duke of Saxony", whether or not they actually ruled any territory.

The first Duchy of Saxe-Eisenach was created in 1596, after the banned Duke John Frederick II had died in captivity and his surviving sons had come of age.

He had to share this, however, with his younger brother John George, who finally accepted the receipt of an income from the duchy of Saxe-Eisenach and made his residence in the small town of Marksuhl.

Saxe-Eisenach assumed its final shape in 1672, following the death of Frederick William III of Saxe-Altenburg and the partition of his lands.