Anna Magdalena Wilcke (or Wilcken or Wülcken) was born into a musical family. Her father Johann Caspar Wilcke was a trumpet player at the courts of Zeitz and Weissenfels, and her mother's father was an organist. By 1721 she was working as a singer in Köthen, where Johann Sebastian Bach was Kapellmeister.
She married J.S. Bach that year, 18 months following the death of his first wife. Together they raised the children from his first marriage and had 13 more children of their own, including the future composers Johann Christoph Friedrich Bach and Johann Christian Bach. Anna Magdalena Bach assisted her husband in his work as Kantor of Leipzig, copying and transcribing the many compositions he wrote for the city's five major churches. He dedicated several keyboard and chamber pieces to her. She is forever associated with the two-volume collection of music known popularly as Anna Magdalena's Notebook, which he wrote for her.