Marie was born in the Chateau de Cuffy, France on 25 March 1491, the eldest child of Jean d'Albret, Sire of Orval, Governor of Champagne, and Charlotte of Nevers, Countess of Rethel.

Her paternal grandparents were Arnaud Amanieu d'Albret, Sire d'Orval (died 1463) and Isabelle de La Tour d'Auvergne (died 8 September 1488), daughter of Bertrand V de La Tour, Count of Auvergne and Boulogne and Jacquette du Peschin.

Marie's paternal great-great-grandfather was Charles d'Albret, Constable of France, who was killed while commanding the French troops at the Battle of Agincourt in 1415.

Marie became the sovereign Countess of Rethel at the age of nine upon the death of her mother, Charlotte, at the Chateau de Meillan-en-Berry, who had herself held the suo jure title.

In 1539, she took the title of Duchess of Nevers, although in point of fact, her son Francis was the suo jure duke.