Anna was a daughter of Landgrave Philip I of Hesse (1501–1567) from his marriage to Princess Christine of Saxony (1505–1549), a daughter of Duke George of Saxony.

She married on 24 February 1544 with Count Palatine Wolfgang of Zweibrücken (1526–1569).

After the death of her husband, Anna and her brother William and Elector Palatine Louis VI jointly acted as guardians for her children.

Anna died in 1591 and was buried in the Lutheran Church of Meisenheim Castle.

Anna was constantly pregnant during much of her marriage, giving birth to thirteen children in just eighteen years.