At age 13 Elisabeth Christine became engaged to the future Charles VI, Holy Roman Emperor through negotiations between her ambitious grandfather, Anthony Ulrich, Duke of Brunswick-Wolfenbüttel and Charles' sister-in-law, Empress Wilhelmina Amalia, whose father was John Frederick, Duke of Brunswick-Lüneburg and thus belonged to another branch of the Guelph dynasty.
However, the Protestant bride opposed the marriage at first, since it involved her switching to Catholicism, but finally she gave in and on 1 May 1707, was converted in Bamberg, Germany.
At the time of the wedding, Charles was fighting for his rights to the Spanish throne against the French-born King Philip V of Spain, so he was living in Barcelona. Elisabeth Christine arrived in Spain on July 1708 and married Charles on 1 August 1708 in the church of Santa Maria del Mar in Barcelona. When her husband left for Vienna to take possession of the imperial crown in 1711, he left Elisabeth Christine behind in Barcelona appointing her as General Governor of Catalonia during his absence. She wisely ruled Catalonia alone until 1713, when she had to leave Barcelona and join her husband in Vienna. Later, they had two children who survived infancy, Empress Maria Theresa and Archduchess Maria Anna.