On 2 February 1675 in Wolfenbüttel, she married Prince Johann Georg of Mecklenburg-Schwerin (1629-1675), son of Adolphus Frederick I, Duke of Mecklenburg-Schwerin and Anna Maria of Ostfriesland, but he died accidentally poisoned five months later.

After her husband's death, she sided with her stepson Ernest Louis I and his minister von Wolzogen, in his quest for sole rulership, ignoring the wish in Bernard I's testament that his sons share power.

This led to 30 years of fraternal strife, during which Elisabeth Eleanor supported her stepson Ernest Louis, against her own son Anton Ulrich.

During Ernest Louis I's rule, Meiningen developed into a centre of musical culture; this is largely due to Elisabeth Eleonore.

The family strife caused her to retreat from public life and concern herself more with religion.