She and her sister Maria Theresa were the only children of Charles VI, Holy Roman Emperor, and Elisabeth Christine of Brunswick to survive into adulthood.

An alliance of Spain and Austria was signed on 30 April 1725 and thus guaranteed the Pragmatic Sanction of 1713, allowing Maria Theresa right of her father's lands being his eldest daughter.

Weeks after the marriage, the couple was 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 Wuustwezel, a town in the Austrian Netherlands, on 24 March where they were met by Count Karl Ferdinand von Königsegg-Erps.

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.

On 9 October 1744 Maria Anna went into labour and gave birth to a stillborn daughter; she never recovered and died 16 December 1744 as after-effect to the difficult childbirth.