She was the maternal granddaughter of Ferdinand I, Holy Roman Emperor and Anna of Bohemia and Hungary, and sister of John William, Duke of Jülich-Cleves-Berg.

Her maternal aunt Anne of Cleves was, for six months, the fourth wife of King Henry VIII of England.

While her father was a Roman Catholic, Marie Eleonore displayed firm Lutheran sympathies early on in wich she were supported by her paternal aunt Amalia who had also helped raising her and her sisters.

Her new husband who had displayed sign of mental illness since 1572, had twice tried to commit suicide and was prone to violent outbursts and also held great fear of " Turks and Muscovites " overrunning Germany.

In 1577, her mentally ill spouse was placed under the regency of his cousin George Frederick, Margrave of Brandenburg-Ansbach, which made the position of Marie Eleonore more difficult at the Ducal court of Königsberg.