Of her six siblings, only she and two older sisters survived to adulthood: Elisabeth Auguste and Maria Anna.

Her father was the designated successor both of his own father Theodore Eustace, Count Palatine of Sulzbach and of his father-in-law Charles III Philip, Elector Palatine, but he never took possession of his inheritance due to his early death in 1729.

After the death of Charles Theodore in February 1799 without surviving legitimate offspring, the Palatinate and Bavaria were inherited by Maria Franziska's youngest son Maximilian IV Joseph (later King Maximilian I of Bavaria); thus, Maria Franziska became the ancestor of all the Bavarian Kings until 1918 and the still living royal branch of the Wittelbachs.

On 6 February 1746, Maria Franziska married Frederick Michael, Count Palatine of Zweibrücken-Birkenfeld.

She was then confined to a semi-detention in a series of monasteries, firstly at the Ursuline in Metz and then to the Augustinians of Bonnevoie in the Duchy of Luxembourg.