She fell in love with Charles Alexander of Lorraine, the younger brother of Maria Theresa's husband, Francis Stephen. There was a lot of resistance against a marriage, not in the least the wish of her father for a politically more important son-in-law.
Maria Anna's husband-to-be was a half-second-cousin-once-removed, being a third generation descendant of Ferdinand III, Holy Roman Emperor, through two of Ferdinand III's children, Leopold I, Holy Roman Emperor and his half-sister Eleonora Maria of Austria.
It was only after their father's death that Elizabeth Christine of Brunswick-Wolfenbüttel gave the approval for the marriage, which was concluded in St Augustine's Church (Augustinerkirche) in Vienna on 7 January 1744. The marriage was recognised by Letters Patent signed on 8 January.
Weeks after the marriage, the couple were appointed governors of the Austrian Netherlands in succession of their aunt Archduchess Maria Elisabeth of Austria, who had died in 1741. The couple left Vienna on 3 February and arrived in Westwezel, a town in the Austrian Netherlands, on 24 March where they were met by Karl Ferdinand von Königsegg-Erps. Karl Ferdinand was a member of the Supreme council of the Netherlands and had to receive Prince Charles and Maria Anna due to etiquette. Their arrival was greeted with much celebration. A ceremony had been organised for their arrival; this included a Te Deum and a collection of balls and banquets.
The couple only had two months of time together in the Netherlands, as Charles had to leave to participate in the war against Prussia, while Maria Anna, pregnant with their first child, remained in Brussels. Charles left officially on 4 May. While alone in Brussels, Maria Anna was helped by the Austrian statesman Count Wenzel Anton Kaunitz-Rietberg.
In October 1744, at the Palais de Charles-Alexandre de Lorraine Maria Anna went into labour and gave birth to a stilborn child; she never recovered and died on 16 December 1744 due to the difficult childbirth. Both were buried in the Imperial Crypt in Vienna. Charles Alexander never remarried.
Charles would remain the Governor until his death in 1780. He was a very popular governor and died in Brussels like his wife.