Born at the Château de Deneuvre, she was the third child and second daughter of Francis I, Duke of Lorraine and Christina of Denmark.

Dorothea was named after her maternal aunt and she was born crippled or lame, which was attributed to the stress of her mother during the pregnancy (her father died one month after her birth, on 12 June 1545).

During the visit of her maternal aunt and uncle in 1551, she and her sister were described: Dorothea was described as having a certain charm and gaiety which made her brother and his family devoted to her.

She helped her brother design the terraced gardens, adorned with fountains and orangeries, in the precincts of the ducal palace: he named a bell in the new clock-tower of Nancy from 1577 after her.

On 26 November 1575 at Nancy, she married Eric II, Duke of Brunswick-Lüneburg, an old friend of her family and a recent widower from an unfortunate marriage with Sidonie of Saxony.