As the heir of her father, she was arranged to marry Ulrik Frederik Gyldenløve, Count of Laurvig, the illegitimate son of the king by her relative Regitze, widow of the illegitimate son of king Christian IV of Denmark and Karen Andersdatter. She followed her first spouse to Oslo in Norway in 1664. She had relationships with her husband's secretary Joachim Lambert, the Frenchman Blanquefort and her brother-in-law Stygge Høeg. In 1667, the spouses separated. As adultery was punishable by death, she thanked her spouse for her life, as he had chosen not to have her killed. She was divorced by permission of the king in 1670, and was allowed to remarry and keep her fortune. In 1673, her father arranged a new marriage with Palle Dyre. In 1690, when she had a relationship with the younger coachman Søren Sørensen Møller, her father asked the king for permission to desinherit her and to have her locked up for the rest of her life. The king asked her spouse for his wishes, and he answered that he only wished for a divorce. She was put under house arrest until the divorce was completed, after which she was desinherited and lost her right to marry in Denmark. She then married her lover Søren Sørensen Møller in Holsten in Germany instead. The couple lived in poverty until they were given a home near Stubbekøbing on Falster by the Queen dowagerCharlotte Amalie of Hesse-Kassel. After the death of the queen dowager in 1714, she lived on charity. She once said to Ludvig Holberg, that she was happier with her third spouse than she had been with any other.
Marie Grubbe has inspired many artists since Ludvig Holberg. She has inspired the books Kysse-Marie by Juliane Preisler (1994), Blichers Brudstykker af en Landsbydegns Dagbog by Steen Steensen (1824), Fru Marie Grubbe by J. P. Jacobsen, (1876) and Hønse-Grethes Familie by H. C. Andersen (1869), the opera Marie Grubbe by Ebbe Hamerik (1940) and a play by Sven Lange. In 1989/1990, a three-episode TV mini-series with the title Marie Grubbe has been produced in GDR-Polish-Hungarian-Danish co-production, directed by Christian Steinke, starring Austrian actress Mijou Kovacs as Marie Grubbe.
Musens sang, Den allersidste dans, Pige træd varsomt, Å hvor jeg, ih, hvor jeg, uh hvor jeg vil, I dit korte liv, Man binder os på mund og hånd, Alle går rundt og forelsker sig, Gå ud og gå en tur, Glemmer du, Titte til hinanden, Drømmeland & Gå med i lunden (Kai Normann Andersen)